Protein Information

Name complex I
Synonyms 39kD; CI 39kD; Complex I; Complex I 39kD; NADH dehydrogenase (ubiquinone) Fe S protein 2 like; NADH ubiquinone oxidoreductase 39 kDa subunit mitochondrial; NADH ubiquinone oxidoreductase 39 kDa subunit; NDUFA 9…

Compound Information

Name rotenone
CAS

Reference List

PubMed Abstract RScore(About this table)
15890011 Zeevalk GD, Bernard LP: Energy status, ubiquitin proteasomal function, and oxidative stress during chronic and acute complex I inhibition with rotenone in mesencephalic cultures. Free Radic Biol Med. 1997;22(3):439-46.
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16464752 Zhang X, Rojas JC, Gonzalez-Lima F: Methylene blue prevents neurodegeneration caused by rotenone in the retina. Eur J Cancer. 1997 Mar;33(3):421-4.

Rotenone is a widely used pesticide that inhibits complex I, the first enzyme of the mitochondrial respiratory chain.
88(1,1,2,3) Details
17241123 Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, Matsuno-Yagi A, Miller GW, Greenamyre JT: Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J Biol Chem. 2005 May 20;280(20):19911-24. Epub 2005 Mar 11.

The pesticide rotenone (ROT) inhibits complex I and reproduces features of PD in animal models, suggesting that environmental agents that inhibit complex I may contribute to PD.
87(1,1,1,7) Details
18685029 Costa C, Belcastro V, Tozzi A, Di Filippo M, Tantucci M, Siliquini S, Autuori A, Picconi B, Spillantini MG, Fedele E, Pittaluga A, Raiteri M, Calabresi P: Electrophysiology and pharmacology of striatal neuronal dysfunction induced by mitochondrial complex I inhibition. J Neurosci. 2008 Aug 6;28(32):8040-52.

The pesticide rotenone inhibits mitochondrial complex I and reproduces features of these basal ganglia neurological disorders in animal models.
83(1,1,1,3) Details
16864419 Zhang X, Jones D, Gonzalez-Lima F: Neurodegeneration produced by rotenone in the mouse retina: a potential model to investigate environmental pesticide contributions to neurodegenerative diseases. Ann N Y Acad Sci. 2003 Jun;991:111-9.

Rotenone is a widely used pesticide and fish toxin that inhibits complex I of the mitochondrial respiratory chain.
83(1,1,1,3) Details
14727190 Gonzalez-Halphen D, Maslov DA: NADH-ubiquinone oxidoreductase activity in the kinetoplasts of the plant trypanosomatid Phytomonas serpens. Biokhimiia. 1989 Sep;54(9):1571-5.

Rotenone at 2-10 microM inhibited the activity 50-75%, indicating that it belongs to respiratory complex I.
83(1,1,1,3) Details
12702446 Veiga A, Arrabaca JD, Sansonetty F, Ludovico P, Corte-Real M, Loureiro-Dias MC: Energy conversion coupled to cyanide-resistant respiration in the yeasts Pichia membranifaciens and Debaryomyces hansenii. Mol Pharmacol. 1995 Nov;48(5):928-37.

In both yeasts the presence of complex I was confirmed by the inhibition of oxygen consumption in isolated mitochondria by rotenone.
82(1,1,1,2) Details
19767442 Drechsel DA, Patel M: Differential contribution of the mitochondrial respiratory chain complexes to reactive oxygen species production by redox cycling agents implicated in parkinsonism. Proc Natl Acad Sci U S A. 1970 Mar;65(3):763-70.

Interestingly, at micromolar (< or = 300 microM) concentrations, PQ-induced H2O2 production was unaffected by complex I inhibition via rotenone, whereas DQ-induced H2O2 production was equally attenuated by inhibition of complex I or III.
82(1,1,1,2) Details
14529466 Kotake Y, Ohta S: MPP+ analogs acting on mitochondria and inducing neuro-degeneration. Biochim Biophys Acta. 2004 Oct 4;1658(3):212-24.

Spectroscopic analyses and structure-activity relationship studies have indicated that the V-shaped structure of the rotenone molecule is critical for binding to the rotenone binding site on complex I.
87(1,1,1,7) Details
19158951 Fink BD, O'Malley Y, Dake BL, Ross NC, Prisinzano TE, Sivitz WI: Mitochondrial targeted coenzyme Q, superoxide, and fuel selectivity in endothelial cells. Free Radic Biol Med. 2007 Mar 1;42(5):642-53. Epub 2006 Dec 14.

In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I.
87(1,1,2,2) Details
12180978 Kotlyar AB, Borovok N: NADH oxidation and NAD+ reduction catalysed by tightly coupled inside-out vesicles from Paracoccus denitrificans. Biochim Biophys Acta. 1998 Jul 20;1365(3):443-52.

Inhibition of the bacterial complex I by a specific inhibitor of Q reduction, rotenone, is very different from that of the mitochondrial enzyme.
83(1,1,1,3) Details
17705834 Jin J, Davis J, Zhu D, Kashima DT, Leroueil M, Pan C, Montine KS, Zhang J: Identification of novel proteins affected by rotenone in mitochondria of dopaminergic cells. J Bioenerg Biomembr. 2010 Mar 19.

Rotenone, a specific inhibitor of mitochondrial complex I, has been shown to produce neurodegeneration in rats as well as in many cellular models that closely resemble PD.
83(1,1,1,3) Details
11516165 Zhang JG, Tirmenstein MA, Nicholls-Grzemski FA, Fariss MW: Mitochondrial electron transport inhibitors cause lipid peroxidation-dependent and -independent cell death: protective role of antioxidants. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2007-11. Epub 2009 Jan 27.

The toxic effects of mitochondrial complex I and II inhibitors, rotenone (ROT) and thenoyltrifluoroacetone (TTFA), respectively, were dependent on oxidative stress and lipid peroxidation, while cell death induced by inhibitors of complexes III and IV, antimycin A (AA) and cyanide (CN), respectively, was caused by MMP collapse and loss of cellular ATP.
82(1,1,1,2) Details
17916065 Muller FL, Liu Y, Abdul-Ghani MA, Lustgarten MS, Bhattacharya A, Jang YC, Van Remmen H: High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I- and complex II-linked substrates. Neuroscience. 2007 Apr 25;146(1):350-65. Epub 2007 Mar 7.

Superoxide production with glutamate+succinate remained high even at low substrate concentrations (<1 mM), was decreased by rotenone and was completely eliminated by FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), indicating that it must in large part originate from reverse-electron transfer through complex I.
82(1,1,1,2) Details
11311359 Jenner P: Parkinson's disease, pesticides and mitochondrial dysfunction. Free Radic Biol Med. 2006 Jul 1;41(1):154-64. Epub 2006 Apr 4.

Selective nigral degeneration with inclusion formation provoked by systemic administration of the herbicide rotenone, through inhibition of complex I, raises the question of pesticide exposure and environmental factors in general, as a cause of Parkinson's disease (PD).
82(1,1,1,2) Details
18445136 Kilbride SM, Telford JE, Tipton KF, Davey GP: Partial inhibition of complex I activity increases Ca-independent glutamate release rates from depolarized synaptosomes. J Neurosci. 2000 Aug 1;20(15):5715-23.

Following a 40% inhibition of complex I activity with rotenone, it was found that Ca (2+)-independent release of glutamate increased from synaptosomes depolarized with 4-aminopyridine.
87(1,1,1,7) Details
9191778 Carelli V, Ghelli A, Ratta M, Bacchilega E, Sangiorgi S, Mancini R, Leuzzi V, Cortelli P, Montagna P, Lugaresi E, Degli Esposti M: Leber's hereditary optic neuropathy: biochemical effect of 11778/ND4 and 3460/ND1 mutations and correlation with the mitochondrial genotype. Mol Microbiol. 2000 Jan;35(2):428-34.

The enzymatic activities of mitochondrial complex I and its sensitivity to the potent inhibitors rotenone and rolliniastatin-2 were studied in mitochondrial particles from platelets, in correlation with mtDNA analysis of platelets and leukocytes.
87(1,1,2,2) Details
11854175 Wong A, Cavelier L, Collins-Schramm HE, Seldin MF, McGrogan M, Savontaus ML, Cortopassi GA: Differentiation-specific effects of LHON mutations introduced into neuronal NT2 cells. Hum Mol Genet. 2002 Feb 15;11(4):431-8.

Differentiation of the cells to the neuronal form also resulted in significant increases in ROS production in the LHON-NT2 neurons versus controls, which is abolished by rotenone, a specific inhibitor of Complex I.
83(1,1,1,3) Details
411483 Crowder SE, Ragan CI: Effects of proteolytic digestion by chymotrypsin on the structure and catalytic properties of reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase from bovine heart mitochondria. Biochem J. 1978 Sep 15;174(3):783-90.

Incubation of NADH-ubiquinone oxidoreductase (Complex I) with chymotrypsin caused loss of rotenone-sensitive ubiquinone-1 reduction and an increase in rotenone-insensitive ubiquinone reduction. 2.
83(1,1,1,3) Details
18436790 Zmijewski JW, Lorne E, Zhao X, Tsuruta Y, Sha Y, Liu G, Siegal GP, Abraham E: Mitochondrial respiratory complex I regulates neutrophil activation and severity of lung injury. Br J Pharmacol. 2007 Apr;150(8):1031-43. Epub 2007 Mar 5.

MEASUREMENTS AND MAIN RESULTS: Inhibition of complex I with either rotenone or the antihyperglycemic agent metformin was associated with increased intracellular levels of both superoxide and hydrogen peroxide, as well as inhibition of LPS-induced I kappaB-alpha degradation, NF-kappaB nuclear accumulation, and proinflammatory cytokine production.
196(2,3,3,6) Details
12628295 Farge G, Touraille S, Debise R, Alziari S: The respiratory chain complex thresholds in mitochondria of a Drosophila subobscura mutant strain. Can J Microbiol. 2006 Apr;52(4):317-27.

Complex I, III and IV activities were inhibited by rotenone, antimycin and KCN, respectively.
86(1,1,1,6) Details
12485407 Sipos I, Tretter L, Adam-Vizi V: Quantitative relationship between inhibition of respiratory complexes and formation of reactive oxygen species in isolated nerve terminals. Autoimmunity. 1999;30(1):43-51.

For inhibition of complex I, III and IV, rotenone, antimycin and cyanide were used, respectively, and ROS formation was followed by measuring the activity of aconitase enzyme.
85(1,1,1,5) Details
19416678 Belcastro V, Tozzi A, Tantucci M, Costa C, Di Filippo M, Autuori A, Picconi B, Siliquini S, Luchetti E, Borsini F, Calabresi P: A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity. Biochem Biophys Res Commun. 1993 Feb 15;190(3):1090-6.

Thus, utilizing extracellular and intracellular recordings from corticostriatal brain slices, we have tested the possible neuroprotective action of two A2A receptor antagonists, ST1535 and ZM241385, on the irreversible electrophysiological effects induced by the acute application of rotenone, a pesticide acting as a selective inhibitor of mitochondrial complex I activity.
83(1,1,1,3) Details
16439141 Betarbet R, Canet-Aviles RM, Sherer TB, Mastroberardino PG, McLendon C, Kim JH, Lund S, Na HM, Taylor G, Bence NF, Kopito R, Seo BB, Yagi T, Yagi A, Klinefelter G, Cookson MR, Greenamyre JT: Intersecting pathways to neurodegeneration in Parkinson's disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Exp Neurol. 2004 Apr;186(2):235-41.

To further evaluated PD pathogenesis here, we used in vivo and in vitro models of chronic low-grade complex I inhibition with the pesticide rotenone.
83(1,1,1,3) Details
9237684 Genova ML, Bovina C, Marchetti M, Pallotti F, Tietz C, Biagini G, Pugnaloni A, Viticchi C, Gorini A, Villa RF, Lenaz G: Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats. Biochem Pharmacol. 2002 Apr 1;63(7):1259-72.
193(2,3,3,3) Details
12840017 Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ: Production of reactive oxygen species by mitochondria: central role of complex III. Antioxid Redox Signal. 2008 Aug;10(8):1435-47.

In contrast to intact mitochondria, blockade of complex I with rotenone markedly increased H2O2 production from submitochondrial particles oxidizing the complex I substrate NADH.
166(2,2,2,6) Details
16141438 Richardson JR, Quan Y, Sherer TB, Greenamyre JT, Miller GW: Paraquat neurotoxicity is distinct from that of MPTP and rotenone. . Synapse. 2010 Mar;64(3):241-50.

We have also demonstrated the requirement for complex I inhibition and oxidative damage in the dopaminergic neurodegeneration produced by rotenone.
163(2,2,2,3) Details
16895522 Sherwood S, Hirst J: Investigation of the mechanism of proton translocation by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria: does the enzyme operate by a Q-cycle mechanism?. Arch Biochem Biophys. 1997 Jan 1;337(1):69-74.

Unexpectedly, in the presence of NADH, complex I inhibited by either rotenone or piericidin A was found to catalyse the exchange of redox states between different quinone and quinol species, providing a possible route for future investigations into the mechanism of energy transduction.
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8126004 Alves PC, Videira A: Disruption of the gene coding for the 21.3-kDa subunit of the peripheral arm of complex I from Neurospora crassa. J Neurosci. 2003 Jul 16;23(15):6181-7.

We observed similar rates of rotenone-sensitive NADH:ubiquinone oxido-reductase activity in mitochondrial membranes from the mutant and wild-type strains and discuss the possibility that this electron transfer is independent of the more hydrophobic part of complex I.
85(1,1,1,5) Details
15906144 Ohnishi ST, Ohnishi T, Muranaka S, Fujita H, Kimura H, Uemura K, Yoshida K, Utsumi K: A possible site of superoxide generation in the complex I segment of rat heart mitochondria. J Neurosci. 2009 Jul 15;29(28):9002-10.

In the forward electron transfer, a slow superoxide production in the presence of glutamate and malate was enhanced by both rotenone and piericidin A (specific inhibitors at the end of the complex I respiratory chain).
83(1,1,1,3) Details
16962686 Biehlmaier O, Alam M, Schmidt WJ: A rat model of Parkinsonism shows depletion of dopamine in the retina. . Eur J Biochem. 1999 Oct 1;265(1):86-93.

Systemic inhibition of complex I (rotenone) in rats has been proposed as a model of PD.
163(2,2,2,3) Details
12496265 Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP: Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Acta Pharmacol Sin. 2004 Mar;25(3):385-9.

Inhibition of mitochondrial respiratory chain complex I by rotenone had been found to induce cell death in a variety of cells.
162(2,2,2,2) Details
17611283 Yadava N, Nicholls DG: Spare respiratory capacity rather than oxidative stress regulates glutamate excitotoxicity after partial respiratory inhibition of mitochondrial complex I with rotenone. Mol Cancer Res. 2007 Sep;5(9):923-32.
162(2,2,2,2) Details
10426140 Cock HR, Cooper JM, Schapira AH: Functional consequences of the 3460-bp mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. J Biochem. 1997 Apr;121(4):746-55.

A 60% rotenone-induced decrease in complex I activity was shown to reduce ATP synthesis in normal fibroblasts, indicating that this level of complex I activity was below the threshold required to affect ATP synthesis.
85(1,1,1,5) Details
9096412 Gutierres S, Sabar M, Lelandais C, Chetrit P, Diolez P, Degand H, Boutry M, Vedel F, de Kouchkovsky Y, De Paepe R: Lack of mitochondrial and nuclear-encoded subunits of complex I and alteration of the respiratory chain in Nicotiana sylvestris mitochondrial deletion mutants. Neurosci Lett. 1995 Feb 17;186(2-3):99-102.

The remaining activity was much less sensitive to rotenone, indicating the breakdown of Complex I activity.
85(1,1,1,5) Details
11798025 Greenamyre JT, Sherer TB, Betarbet R, Panov AV: Complex I and Parkinson's disease. Brain Res Bull. 2010 Mar 16;81(4-5):484-90. Epub 2009 Oct 23.

Recent experimental work has modeled this abnormality using rotenone to systemically inhibit complex I.
85(1,1,1,5) Details
20100453 Batista AP, Fernandes AS, Louro RO, Steuber J, Pereira MM: Energy conservation by Rhodothermus marinus respiratory complex I. . J Neurochem. 2003 Mar;84(5):1193-200.

Specific inhibitors of complex I (rotenone) and of the dioxygen reductase (KCN) inhibited the proton and the sodium ion transport, but the KCN effect was totally reverted by the addition of menaquinone analogues, indicating that both transports were catalyzed by complex I.
83(1,1,1,3) Details
10386974 Chinopoulos C, Tretter L, Adam-Vizi V: Depolarization of in situ mitochondria due to hydrogen peroxide-induced oxidative stress in nerve terminals: inhibition of alpha-ketoglutarate dehydrogenase. PLoS One. 2009;4(1):e4250. Epub 2009 Jan 22.

When complex I of the respiratory chain was inhibited by rotenone (2 microM), delta psi (m) was unaltered, but on subsequent addition of H2O2, delta psi (m) started to decrease and collapsed during incubation with 0.5 mM H2O2 for 12 min.
83(1,1,1,3) Details
11299009 Bykova NV, Moller IM: Involvement of matrix NADP turnover in the oxidation of NAD-linked substrates by pea leaf mitochondria. Plant Physiol. 1990 Sep;94(1):189-193.

As estimated by the inhibition caused by 5 microM diphenyleneiodonium (DPI) in the presence of rotenone to inhibit complex I, the activity of NDin (NADPH) during glycine oxidation (measured both as O2 uptake and as CO2 release) was 40-50 nmol mg-1 protein min-1.
162(2,2,2,2) Details
12177198 Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT: An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. Sleep. 2007 Apr 1;30(4):413-25.

Chronic systemic complex I inhibition caused by rotenone exposure induces features of Parkinson's disease (PD) in rats, including selective nigrostriatal dopaminergic degeneration and formation of ubiquitin- and alpha-synuclein-positive inclusions (Betarbet et al., 2000).
162(2,2,2,2) Details
12411515 Hanley PJ, Ray J, Brandt U, Daut J: Halothane, isoflurane and sevoflurane inhibit NADH:ubiquinone oxidoreductase (complex I) of cardiac mitochondria. Biochim Biophys Acta. 1993 Mar 1;1141(2-3):262-8.

Unlike the classical inhibitor rotenone, none of the anaesthetics completely inhibited enzyme activity at high concentration, suggesting that these agents bind weakly to the 'hydrophobic inhibitory site' of complex I.
85(1,1,1,5) Details
18358763 Dlaskova A, Hlavata L, Jezek J, Jezek P: Mitochondrial Complex I superoxide production is attenuated by uncoupling. Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1110-6.

It also partially prevented suppression by FCCP of rotenone-induced H (2) O (2) production with Complex I substrates alone (glutamate and malate), but nearly completely with Complexes I and II substrates.
85(1,1,1,5) Details
18077608 Chen Q, Moghaddas S, Hoppel CL, Lesnefsky EJ: Ischemic defects in the electron transport chain increase the production of reactive oxygen species from isolated rat heart mitochondria. Physiol Plant. 2004 Mar;120(3):370-385.

Inhibition of complex I with rotenone increased H (2) O (2) production by 179 +/- 24% and 155 +/- 14% in SSM and IFM, respectively, following ischemia.
83(1,1,1,3) Details
9593904 Degli Esposti M: Inhibitors of NADH-ubiquinone reductase: an overview. Hum Mol Genet. 2004 Apr 1;13(7):669-81. Epub 2004 Feb 12.

The inhibitors are presented within the broad categories of natural and commercial compounds and their potency is related to that of rotenone, the classical inhibitor of complex I.
83(1,1,1,3) Details
9131045 Grivennikova VG, Maklashina EO, Gavrikova EV, Vinogradov AD: Interaction of the mitochondrial NADH-ubiquinone reductase with rotenone as related to the enzyme active/inactive transition. J Biol Chem. 1994 Aug 19;269(33):21037-42.

The interaction of rotenone with active ('pulsed') and thermally de-activated ('resting') membrane-bound Complex I (Kotlyar, A.B. and Vinogradov, A.D. (1990) Biochim.
162(2,2,2,2) Details
15347666 Lesnefsky EJ, Chen Q, Moghaddas S, Hassan MO, Tandler B, Hoppel CL: Blockade of electron transport during ischemia protects cardiac mitochondria. Neurobiol Dis. 2009 Feb;33(2):182-92. Epub 2008 Oct 26.

Isolated, perfused rabbit hearts were treated with rotenone, an irreversible inhibitor of complex I in the proximal electron transport chain, immediately before ischemia.
162(2,2,2,2) Details
7735172 Charalambous A, Mangner TJ, Kilbourn MR: Synthesis of (2-[11C] methoxy) rotenone, a marker of mitochondrial complex I activity. Neuropharmacology. 2008 Dec;55(8):1340-6. Epub 2008 Sep 10.

Rotenone is a potent reversible competitive inhibitor of complex I (NADH-CoQ reductase).
143(1,3,3,3) Details
9684860 Darrouzet E, Issartel JP, Lunardi J, Dupuis A: The 49-kDa subunit of NADH-ubiquinone oxidoreductase (Complex I) is involved in the binding of piericidin and rotenone, two quinone-related inhibitors. Chem Biol Interact. 2001 Dec 21;138(3):267-84.
84(1,1,1,4) Details
16584707 Borutaite V, Brown GC: S-nitrosothiol inhibition of mitochondrial complex I causes a reversible increase in mitochondrial hydrogen peroxide production. Biochim Biophys Acta. 2006 May-Jun;1757(5-6):562-6. Epub 2006 Mar 23.

Specific inhibition of complex I with rotenone increased H2O2 production to a similar extent as that caused by SNAP.
84(1,1,1,4) Details
16678117 Grivennikova VG, Vinogradov AD: Generation of superoxide by the mitochondrial Complex I. . Plant Physiol. 2000 Nov;124(3):1239-50.

The succinate-supported production was inhibited by rotenone and uncouplers, showing that most part of superoxide produced during succinate oxidation is originated from univalent oxygen reduction by Complex I.
83(1,1,1,3) Details
11245783 Prieur I, Lunardi J, Dupuis A: Evidence for a quinone binding site close to the interface between NUOD and NUOB subunits of Complex I. FEBS Lett. 1999 May 28;451(3):347-50.

Piericidin, rotenone and pyridaben are specific inhibitors of the NADH-ubiquinone oxidoreductase (Complex I) that bind to its ubiquinone binding site (s).
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1521539 Menz RI, Griffith M, Day DA, Wiskich JT: Matrix NADH dehydrogenases of plant mitochondria and sites of quinone reduction by complex I. Ann Neurol. 1991 Nov;30(5):701-8.

We confirm that there are two dehydrogenases capable of oxidising internal NADH and that only one of these, namely complex I, is inhibited by rotenone.
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15571245 Gattermann N, Dadak M, Hofhaus G, Wulfert M, Berneburg M, Loeffler ML, Simmonds HA: Severe impairment of nucleotide synthesis through inhibition of mitochondrial respiration. Eur J Biochem. 1994 Nov 15;226(1):237-42.

This was surprising since Rotenone inhibits complex I of the respiratory chain, which is upstream of ubiquinone where DHODH interacts with the RC.
118(1,2,3,3) Details
8656275 Higgins DS Jr, Greenamyre JT: [3H] dihydrorotenone binding to NADH: ubiquinone reductase (complex I) of the electron transport chain: an autoradiographic study. Exp Parasitol. 2002 Jan;100(1):54-61.

In skeletal muscle, heart, and kidney, binding was less affected by NADH. [3H] DHR binding is inhibited by rotenone (IC50 = 8-20 nM), meperidine (IC50 = 34-57 microM), amobarbitol (IC50 = 375-425 microM), and MPP+ (IC50 = 4-5 mM), consistent with the potencies of these compounds in inhibiting complex I activity.
117(1,2,2,7) Details
17477844 Zoccarato F, Cavallini L, Bortolami S, Alexandre A: Succinate modulation of H2O2 release at NADH:ubiquinone oxidoreductase (Complex I) in brain mitochondria. Biochem Biophys Res Commun. 2009 Oct 16;388(2):311-6. Epub 2009 Aug 5.

The much faster succinate-dependent H2O2 production is ascribed to Complex I, being rotenone-sensitive.
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7649309 Vinogradov AD, Sled VD, Burbaev DS, Grivennikova VG, Moroz IA, Ohnishi T: Energy-dependent Complex I-associated ubisemiquinones in submitochondrial particles. Chem Biol Interact. 1995 Oct 20;98(1):1-13.

The g = 2.00 signals from both fast-relaxing SQNf (P1/2 = 170 mW at 40 K) and slow-relaxing SQNs (P1/2 = 0.7 mW) are sensitive to uncouplers, rotenone and thermally induced deactivation of Complex I.
84(1,1,1,4) Details
12237311 St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD: Topology of superoxide production from different sites in the mitochondrial electron transport chain. FEBS Lett. 1995 Aug 14;370(1-2):83-7.

However, when complex I was fully reduced using rotenone, rat mitochondria released significantly more hydrogen peroxide than pigeon mitochondria.
84(1,1,1,4) Details
18615133 Bonsi P, Cuomo D, Martella G, Sciamanna G, Tolu M, Calabresi P, Bernardi G, Pisani A: Mitochondrial toxins in Basal Ganglia disorders: from animal models to therapeutic strategies. J Am Soc Nephrol. 2002 May;13(5):1179-89.

MPTP and rotenone, both selective inhibitors of mitochondrial complex I have been extensively used to mimic PD.
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16120427 Blanco FJ, Lopez-Armada MJ, Maneiro E: Mitochondrial dysfunction in osteoarthritis. . Mitochondrion. 2004 Sep;4(5-6):715-28. Epub 2004 Oct 1.

Inhibition of complex I with rotenone increases the expression and synthesis of Bcl-2 and Cox-2, both effects are similar effects to produced by IL-1 in human chondrocytes.
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11146003 Chinopoulos C, Adam-Vizi V: Mitochondria deficient in complex I activity are depolarized by hydrogen peroxide in nerve terminals: relevance to Parkinson's disease. Ann Neurol. 1999 Mar;45(3):320-8.

Here we demonstrate that the membrane potential of in situ mitochondria (Delta Psi m), as measured by the fluorescence change of JC-l (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbezimidazolyl-carbocyani ne iodide), collapses when isolated nerve terminals are exposed to hydrogen peroxide (H (2) O (2), 100 and 500 microM) in combination with the inhibition of complex I by rotenone (5 nM-1 microM).
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9832155 Hensley K, Pye QN, Maidt ML, Stewart CA, Robinson KA, Jaffrey F, Floyd RA: Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site. J Neural Transm Suppl. 2006;(70):273-6.
115(1,2,2,5) Details
19233273 Silva JM, Wong A, Carelli V, Cortopassi GA: Inhibition of mitochondrial function induces an integrated stress response in oligodendroglia. J Biol Chem. 2003 Sep 26;278(39):37832-9. Epub 2003 Jul 9.

Therefore, we wanted to determine whether mitochondrial dysfunction induced by complex I inhibition with rotenone can activate the ISR, specifically by the ER kinase PERK, in oligodendroglial cells.
84(1,1,1,4) Details
15175007 Lambert AJ, Brand MD: Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Planta. 2006 Jun;224(1):196-204. Epub 2006 Jan 17.

By far, the largest rate of superoxide production was from mitochondria respiring on succinate; this rate was almost abolished by rotenone or piericidin, indicating that superoxide production from complex I is large under conditions of reverse electron transport.
84(1,1,1,4) Details
19664596 Ota S, Horigome K, Ishii T, Nakai M, Hayashi K, Kawamura T, Kishino A, Taiji M, Kimura T: Metformin suppresses glucose-6-phosphatase expression by a complex I inhibition and AMPK activation-independent mechanism. Neurochem Res. 2009 Jun 4.

Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism.
83(1,1,1,3) Details
11936880 Gschwend MH, Rudel R, Strauss WS, Sailer R, Brinkmeier H, Schneckenburger H: Optical detection of mitochondrial NADH content in intact human myotubes. Cell Mol Biol (Noisy-le-grand). 2001;47 Online Pub:OL95-104.

In the absence of the fluorescent mitochondrial marker rhodamine (R123), the NADH autofluorescence (i.e. a signal monitoring cytoplasmic plus mitochondrial NADH) remained unchanged upon inhibition of complex I by rotenone, and was increased by a factor of 2 upon inhibition of complex III by antimycin.
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20143419 Corona JC, Gimenez-Cassina A, Lim F, Diaz-Nido J: Hexokinase II gene transfer protects against neurodegeneration in the rotenone and MPTP mouse models of Parkinson's disease. J Neurosci Res. 2010 Feb 8.

Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibit the mitochondrial complex I and they cause the death of substantia nigra dopaminergic neurons, thereby providing acute murine models of Parkinson's disease.
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16543240 Seo BB, Nakamaru-Ogiso E, Flotte TR, Matsuno-Yagi A, Yagi T: In vivo complementation of complex I by the yeast Ndi1 enzyme. J Neurol Sci. 2004 Aug 30;223(2):149-55.

We have shown previously that the single subunit rotenone-insensitive NADH-quinone oxidoreductase (Ndi1) of Saccharomyces cerevisiae mitochondria can restore NADH oxidation in complex I-deficient mammalian cells.
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11997134 Ventura B, Genova ML, Bovina C, Formiggini G, Lenaz G: Control of oxidative phosphorylation by Complex I in rat liver mitochondria: implications for aging. J Bioenerg Biomembr. 1995 Aug;27(4):397-406.

This indication was strengthened by examining the rotenone inhibition thresholds showing that Complex I becomes more rate controlling, over all the examined activities, during aging.
115(1,2,2,5) Details
10652103 Steuber J, Schmid C, Rufibach M, Dimroth P: Na+ translocation by complex I (NADH:quinone oxidoreductase) of Escherichia coli. Biofactors. 2008;32(1-4):31-9.

With an E. coli mutant deficient in complex I, the Na+ transport activity was low (1-3 nmol mg-1 min-1), and rotenone was without effect.
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8769881 Morikawa N, Nakagawa-Hattori Y, Mizuno Y: Effect of dopamine, dimethoxyphenylethylamine, papaverine, and related compounds on mitochondrial respiration and complex I activity. Biochim Biophys Acta. 2007 May;1772(5):533-42. Epub 2007 Jan 26.

Papaverine was the most potent inhibitor of complex I and NADH-linked mitochondrial respiration among the compounds tested next to rotenone.
84(1,1,1,4) Details
17540903 Reeves MB, Davies AA, McSharry BP, Wilkinson GW, Sinclair JH: Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Biochemistry. 2003 Mar 18;42(10):3032-9.

Using rotenone, a potent inhibitor of the mitochondrial enzyme complex I (reduced nicotinamide adenine dinucleotide-ubiquinone oxido-reductase), we found that human cytomegalovirus infection protected cells from rotenone-induced apoptosis, a protection mediated by a 2.7-kilobase virally encoded RNA (beta2.7).
84(1,1,1,4) Details
10371157 Galkin AS, Grivennikova VG, Vinogradov AD: --> H+/2e- stoichiometry in NADH-quinone reductase reactions catalyzed by bovine heart submitochondrial particles. Biochemistry. 2007 Sep 25;46(38):10971-8. Epub 2007 Aug 31.

Rotenone, piericidin and thermal deactivation of complex I completely prevented NADH-induced proton translocation in the NADH-endogenous ubiquinone reductase reaction.
82(1,1,1,2) Details
20300811 Sanz A, Stefanatos R, McIlroy G: Production of reactive oxygen species by the mitochondrial electron transport chain in Drosophila melanogaster. Toxicol Sci. 2005 Nov;88(1):193-201. Epub 2005 Sep 1.

The production of ROS during reverse electron transport can be prevented either by rotenone or by the oxidation of NADH by complex I.
82(1,1,1,2) Details
15790535 Testa CM, Sherer TB, Greenamyre JT: Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Biochim Biophys Acta. 1999 Jan 6;1453(1):49-62.

Chronic complex I inhibition over weeks by low dose (10-50 nM) rotenone in this system lead to dose- and time-dependent destruction of substantia nigra pars compacta neuron processes, morphologic changes, some neuronal loss, and decreased tyrosine hydroxylase (TH) protein levels.
114(1,2,2,4) Details
14570403 Sipos I, Tretter L, Adam-Vizi V: The production of reactive oxygen species in intact isolated nerve terminals is independent of the mitochondrial membrane potential. Toxicol Sci. 2007 Jan;95(1):163-71. Epub 2006 Oct 3.

In addition, we detected a significant antimycin-induced H2O2 production when the flow of electrons through complex I was inhibited by rotenone, indicating that the respiratory chain of in situ mitochondria in synaptosomes has a substantial electron influx distal from the rotenone site, which could contribute to ROS generation when the complex III is inhibited.
114(1,2,2,4) Details
11164812 Sherer TB, Trimmer PA, Borland K, Parks JK, Bennett JP Jr, Tuttle JB: Chronic reduction in complex I function alters calcium signaling in SH-SY5Y neuroblastoma cells. Brain Res. 2000 Jun 23;868(2):191-201.

A pharmacological model of reduced complex I activity was created by prolonged treatment of SH-SY5Y cells with low doses (5-20 nM) of rotenone, a selective inhibitor of complex I.
84(1,1,1,4) Details
3132077 Ichiki T, Tanaka M, Nishikimi M, Suzuki H, Ozawa T, Kobayashi M, Wada Y: Deficiency of subunits of Complex I and mitochondrial encephalomyopathy. . Am J Physiol Cell Physiol. 2005 Jun;288(6):C1440-50. Epub 2005 Jan 12.

In all patients, the content of subunits of Complex I was also reduced in parallel with the rotenone-sensitive NADH-cytochrome c reductase activity.
84(1,1,1,4) Details
18032788 Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB: Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. Biochim Biophys Acta. 2007 Mar;1767(3):222-32. Epub 2007 Feb 9.

Herein, we determined that inhibitors of complex I (rotenone) and complex II (TTFA) induce cell death and autophagy in the transformed cell line HEK 293, and in cancer cell lines U87 and HeLa.
82(1,1,1,2) Details
8313963 Finel M, Majander A: Studies on the proton-translocating NADH:ubiquinone oxidoreductases of mitochondria and Escherichia coli using the inhibitor 1,10-phenanthroline. Brain Res. 1997 Feb 21;749(1):44-52.

EPR spectroscopy of submitochondrial particles indicates that OP, similarly to rotenone, inhibits electron transfer between the Fe-S clusters of complex I and the ubiquinone pool.
82(1,1,1,2) Details
19073440 King TD, Clodfelder-Miller B, Barksdale KA, Bijur GN: Unregulated mitochondrial GSK3beta activity results in NADH: ubiquinone oxidoreductase deficiency. Am J Physiol Cell Physiol. 2008 Apr;294(4):C945-56. Epub 2008 Jan 30.

Conversely, chemical inhibitors of GSK3beta inhibited MPP+- and rotenone-induced apoptosis, and attenuated the mitochondrial GSK3beta-mediated impairment in complex I.
113(1,2,2,3) Details
18784283 Garmier M, Carroll AJ, Delannoy E, Vallet C, Day DA, Small ID, Millar AH: Complex I dysfunction redirects cellular and mitochondrial metabolism in Arabidopsis. Plant Physiol. 2008 Nov;148(3):1324-41. Epub 2008 Sep 10.

These data demonstrate that, in Arabidopsis cells, complex I inhibition by rotenone induces significant remodeling of metabolic pathways involving the mitochondria and other compartments and point to early metabolic changes in response to mitochondrial dysfunction.
113(1,2,2,3) Details
8037664 Degli Esposti M, Ghelli A, Ratta M, Cortes D, Estornell E: Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I). Front Biosci. 2007 Jan 1;12:1079-93.

The properties of five of such acetogenins are compared with those of rotenone and piericidin, classical potent inhibitors of Complex I.
84(1,1,1,4) Details
15836612 Votyakova TV, Reynolds IJ: Ca2+-induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex I. Mol Biochem Parasitol. 1994 Mar;64(1):87-94.

In this study we investigated the effect of Ca2+ loads on ROS release from rat brain mitochondria with complex I partially inhibited by rotenone.
84(1,1,1,4) Details
12753929 Sousa SC, Maciel EN, Vercesi AE, Castilho RF: Ca2+-induced oxidative stress in brain mitochondria treated with the respiratory chain inhibitor rotenone. FEBS Lett. 2003 May 22;543(1-3):179-83.

Ca (2+)-stimulated mitochondrial ROS release was associated with membrane lipid peroxidation and was directly correlated with the degree of complex I inhibition by rotenone.
82(1,1,1,2) Details
2128595 Wijburg FA, Feller N, de Groot CJ, Wanders RJ: Menadione partially restores NADH-oxidation and ATP-synthesis in complex I deficient fibroblasts. Neurosci Lett. 2003 Nov 6;351(1):29-32.

In this paper we report our studies on the effects of menadione in cultured fibroblasts treated with rotenone to block complex I.
82(1,1,1,2) Details
16219024 Hoglinger GU, Lannuzel A, Khondiker ME, Michel PP, Duyckaerts C, Feger J, Champy P, Prigent A, Medja F, Lombes A, Oertel WH, Ruberg M, Hirsch EC: The mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathy. Eur J Biochem. 1994 Jan 15;219(1-2):691-8.

To determine experimentally whether chronic generalized complex I inhibition has an effect on the distribution of alpha-synuclein or tau, we infused rats systemically with the plant-derived isoflavonoid rotenone.
113(1,2,2,3) Details
11677254 Votyakova TV, Reynolds IJ: DeltaPsi (m)-Dependent and -independent production of reactive oxygen species by rat brain mitochondria. Neurobiol Dis. 2006 May;22(2):404-20. Epub 2006 Jan 24.

Mitochondria respiring on the complex I substrates, glutamate and malate, produce very little ROS until complex I is inhibited with rotenone, which is also consistent with complex I being the major site of ROS generation.
113(1,2,2,3) Details
17011837 Bacsi A, Woodberry M, Widger W, Papaconstantinou J, Mitra S, Peterson JW, Boldogh I: Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells. Biochem J. 1979 Aug 15;182(2):353-60.

In the present study, we identified the site of reactive oxygen species production in mitochondria. 3-NPA increased O2- generation in mitochondria respiring on the complex I substrates pyruvate+malate, an effect fully inhibited by rotenone.
84(1,1,1,4) Details
17702527 Coe KJ, Jia Y, Ho HK, Rademacher P, Bammler TK, Beyer RP, Farin FM, Woodke L, Plymate SR, Fausto N, Nelson SD: Comparison of the cytotoxicity of the nitroaromatic drug flutamide to its cyano analogue in the hepatocyte cell line TAMH: evidence for complex I inhibition and mitochondrial dysfunction using toxicogenomic screening. Free Radic Biol Med. 2003 Jul 1;35(1):24-32.

Comparisons of transcriptomic changes caused by FLU with those caused by a panel of known cytotoxicants [acetaminophen, tetrafluoroethylcysteine, diquat, and rotenone (ROT)] indicated that FLU results in a temporal gene expression pattern similar to ROT, a known inhibitor of complex I of the electron transport chain.
84(1,1,1,4) Details
17320357 Park JS, Li YF, Bai Y: Yeast NDI1 improves oxidative phosphorylation capacity and increases protection against oxidative stress and cell death in cells carrying a Leber's hereditary optic neuropathy mutation. Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1754-60. Epub 2003 Sep 4.

In transformant cell lines, LeNDI1-1 and -2, total and complex I-dependent respiration were fully restored and largely resistant to complex I inhibitor, rotenone, indicating a dominant role of NDI1 in the transfer of electrons in the host cells.
82(1,1,1,2) Details
11346950 Zhang Q, Soole KL, Wiskich JT: Regulation of respiration in rotenone-treated tobacco cell suspension cultures. Eur J Biochem. 1994 Jun 15;222(3):975-82.

Cells of Nicotiana tabacum L. suspension cultures were treated with the respiratory inhibitor rotenone, which specifically inhibits complex I activity of mitochondria.
82(1,1,1,2) Details
10854571 Lamensdorf I, Eisenhofer G, Harvey-White J, Nechustan A, Kirk K, Kopin IJ: 3,4-Dihydroxyphenylacetaldehyde potentiates the toxic effects of metabolic stress in PC12 cells. Cell Death Differ. 2005 Nov;12(11):1417-28.

Here, we examined the potential role of DOPAL in the toxicity induced by complex I inhibition in PC12 cells and compared the effects of rotenone on concentrations of DOPAL and DOPET to those of MPP (+).
113(1,2,2,3) Details
17127363 Gomez C, Bandez MJ, Navarro A: Pesticides and impairment of mitochondrial function in relation with the parkinsonian syndrome. Eur J Neurosci. 2005 Jul;22(1):125-32.

The determination of NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome oxidase activities in rat brain submitochondrial showed again the selective inhibition of Complex I by rotenone and pyridaben, whereas paraquat produced a non-selective inhibition affecting all the respiratory chain complexes.
113(1,2,2,3) Details
1497345 Bironaite DA, Cenas NK, Anusevicius ZJ, Medentsev AG, Akimenko VK, Usanov SA: Fungal quinone pigments as oxidizers and inhibitors of mitochondrial NADH:ubiquinone reductase. FEBS Lett. 1998 Jul 10;431(1):34-8.

The bimolecular rate constants (turnover number (TN)/Km) of rotenone-insensitive reduction of these compounds are in the range of 1.2 x 10 (4)-1.6 x 10 (5) M-1s-1. 2-Oxyjuglone acts as inhibitor of NADH:ferricyanide reductase reaction of complex I (KI = 30 microM).
83(1,1,1,3) Details
16234867 Chen Y, Suzuki I: Effects of electron transport inhibitors and uncouplers on the oxidation of ferrous iron and compounds interacting with ferric iron in Acidithiobacillus ferrooxidans. Am J Respir Crit Care Med. 1995 Jun;151(6):1848-51.

The oxidation rates of Fe2+ and L-cysteine inhibited by complex I and complex III inhibitors (amytal, rotenone, antimycin A, myxothiazol, and HQNO) were stimulated more extensively by uncouplers than the control rates.
83(1,1,1,3) Details
18639366 Jia H, Liu Z, Li X, Feng Z, Hao J, Li X, Shen W, Zhang H, Liu J: Synergistic anti-Parkinsonism activity of high doses of B vitamins in a chronic cellular model. J Biol Chem. 2006 Apr 14;281(15):10143-52. Epub 2006 Jan 12.

Pretreatment with B vitamins (also 4 weeks) prevented rotenone-induced: (1) mitochondrial dysfunction, including reduced mitochondrial membrane potential and activities of complex I; (2) oxidative stress, including increase in reactive oxygen species, oxidative DNA damage and protein oxidation, and (3) Parkinsonism parameters, including accumulation of alpha-synuclein and poly-ubiquitin.
82(1,1,1,2) Details
12935904 Carriere A, Fernandez Y, Rigoulet M, Penicaud L, Casteilla L: Inhibition of preadipocyte proliferation by mitochondrial reactive oxygen species. J Child Neurol. 1991 Apr;6(2):134-42.

Rotenone and oligomycin, inhibitors of complex I and of ATP synthase respectively, increased H (2) O (2) and inhibited cell growth of preadipocytes (without inducing necrosis or apoptosis).
82(1,1,1,2) Details
14515342 Leng A, Feldon J, Ferger B: Rotenone increases glutamate-induced dopamine release but does not affect hydroxyl-free radical formation in rat striatum. J Neurochem. 2001 Jan;76(1):302-6.

To investigate the relationship of free radical formation, complex I inhibition, and dopamine release, rotenone (15 mg/kg s.c.) was injected in male Sprague Dawley rats.
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9125443 Ferrante RJ, Schulz JB, Kowall NW, Beal MF: Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra. Arch Biochem Biophys. 2001 Sep 1;393(1):87-96.

Rotenone is an insecticide which is a specific inhibitor of complex I.
113(1,2,2,3) Details
15936733 Saravanan KS, Sindhu KM, Mohanakumar KP: Acute intranigral infusion of rotenone in rats causes progressive biochemical lesions in the striatum similar to Parkinson's disease. FEBS Lett. 1991 Jul 29;286(1-2):129-32.

Unilateral stereotaxic infusion of rotenone (2-12 mug in 1 mul) into substantia nigra (SN) pars compacta caused significant inhibition of complex-I activity and increased production of hydroxyl radicals in vivo as measured employing spectrophotometric and HPLC-electrochemical procedures, respectively.
112(1,2,2,2) Details
3691507 Nohl H: Demonstration of the existence of an organo-specific NADH dehydrogenase in heart mitochondria. Biochem Pharmacol. 1991 Feb 15;41(4):543-52.

The "exogenous NADH dehydrogenase" of heart mitochondria was found to introduce reducing equivalents into the respiratory chain before the rotenone block, indicating that the enzyme is associated with complex I.
83(1,1,1,3) Details
19913015 Costa C, Tozzi A, Luchetti E, Siliquini S, Belcastro V, Tantucci M, Picconi B, Ientile R, Calabresi P, Pisani F: Electrophysiological actions of zonisamide on striatal neurons: Selective neuroprotection against complex I mitochondrial dysfunction. Nippon Rinsho. 2002 Apr;60 Suppl 4:171-4.

Thus, ZNS was also tested in two different in vitro neurotoxic models obtained by acutely exposing corticostriatal slices either to rotenone, a selective inhibitor of mitochondrial complex I, or to 3-nitropropionic acid (3-NP), an inhibitor of complex II.
83(1,1,1,3) Details
15507238 Li J, Fu P, French BA, French SW: The effect of rotenone on the urinary ethanol cycle in rats fed ethanol intragastrically. J Neurosci. 2002 Feb 1;22(3):782-90.

Rotenone also inhibits complex I and induces a reduced state.
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7926004 Degli Esposti M, Carelli V, Ghelli A, Ratta M, Crimi M, Sangiorgi S, Montagna P, Lenaz G, Lugaresi E, Cortelli P: Functional alterations of the mitochondrially encoded ND4 subunit associated with Leber's hereditary optic neuropathy. Neurosci Lett. 2008 Dec 5;447(1):87-91. Epub 2008 Sep 24.

We report that this amino acid substitution alters the affinity of complex I for the ubiquinone substrate and induces resistance towards its potent inhibitor rotenone in mitochondria of LHON patients.
82(1,1,1,2) Details
18022104 Yalamanchili P, Wexler E, Hayes M, Yu M, Bozek J, Kagan M, Radeke HS, Azure M, Purohit A, Casebier DS, Robinson SP: Mechanism of uptake and retention of F-18 BMS-747158-02 in cardiomyocytes: a novel PET myocardial imaging agent. Toxicol Appl Pharmacol. 1999 Aug 1;158(3):296-302.

METHODS AND RESULTS: Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC (50) of 16.6 +/- 3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC (50) of 18.2 +/- 6.7 nmol/L, 19.8 +/- 2.6 nmol/L, and 23.1 +/- 1.5 nmol/L, respectively).
31(0,1,1,1) Details
11040979 Korkisha OV, Ruuge EK: [Generation of superoxide radicals by heart mitochondria: study by spin trapping under continuous oxygenation]. J Nucl Cardiol. 2007 Nov-Dec;14(6):782-8. Epub 2007 Oct 22.

The inhibition of the reverse electron transport in complex I of the respiratory chain by rotenone (oxidation substrate--succinate) caused a substantial decrease in the rate of O2-. formation by mitochondria.
31(0,1,1,1) Details
11705700 Frantseva MV, Carlen PL, Perez Velazquez JL: Dynamics of intracellular calcium and free radical production during ischemia in pyramidal neurons. Neurotoxicology. 2006 Sep;27(5):826-34. Epub 2006 Apr 28.

Ischemia-induced FR generation was decreased by the mitochondrial complex I blocker, rotenone, indicating that mitochondria are the principal source of ischemic FR production.
31(0,1,1,1) Details
9495873 Brambilla L, Sestili P, Guidarelli A, Palomba L, Cantoni O: Electron transport-mediated wasteful consumption of NADH promotes the lethal response of U937 cells to tert-butylhydroperoxide. J Biol Chem. 1994 Mar 11;269(10):7777-84.

Rotenone mitigated the lethal effects of the hydroperoxide over the same concentration-range in which the complex I inhibitor inhibited oxygen utilization.
31(0,1,1,1) Details
12826253 Servais S, Couturier K, Koubi H, Rouanet JL, Desplanches D, Sornay-Mayet MH, Sempore B, Lavoie JM, Favier R: Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria. Mol Pharmacol. 2002 Jul;62(1):22-9.

Inhibition of H (2) O (2) formation by rotenone suggests that complex I of the electron transport chain is likely the major physiological H (2) O (2)-generating system.
31(0,1,1,1) Details
16313906 Pan T, Li X, Xie W, Jankovic J, Le W: Valproic acid-mediated Hsp70 induction and anti-apoptotic neuroprotection in SH-SY5Y cells. Chem Res Toxicol. 2007 Sep;20(9):1277-90. Epub 2007 Aug 17.

We now show that VPA attenuates rotenone (a potent complex I inhibitor)-induced apoptosis through the induction of heat shock protein 70, which may interact with apoptotic-protease-activating factor 1.
31(0,1,1,1) Details
10200266 Au HC, Seo BB, Matsuno-Yagi A, Yagi T, Scheffler IE: The NDUFA1 gene product (MWFE protein) is essential for activity of complex I in mammalian mitochondria. Neuropharmacology. 2007 Mar;52(3):827-35. Epub 2006 Nov 22.

Complementation with hamster NDUFA1 cDNA restored the rotenone-sensitive complex I activity of these mutant cells to approximately 100% of the parent cell activity.
11(0,0,1,6) Details
11695833 Yagi T, Seo BB, Di Bernardo S, Nakamaru-Ogiso E, Kao MC, Matsuno-Yagi A: NADH dehydrogenases: from basic science to biomedicine. Mol Neurobiol. 2005;31(1-3):81-93.

This project involves attempting to repair complex I defects in the mammalian system using Saccharomyces cerevisiae NDI1 genes, which code for the internal, rotenone-insensitive NADH-quinone oxidoreductase.
10(0,0,1,5) Details
11124957 Grivennikova VG, Kapustin AN, Vinogradov AD: Catalytic activity of NADH-ubiquinone oxidoreductase (complex I) in intact mitochondria. evidence for the slow active/inactive transition. J Neurochem. 2002 Aug;82(3):482-94.

Alamethicin-treated mitochondria catalyzed the rotenone-sensitive NADH-quinone reductase reaction with exogenousely added NADH and quinone-acceptor at the rates expected if the enzyme active sites would be freely accessible for the substrates.
6(0,0,0,6) Details
12626666 Ortega-Saenz P, Pardal R, Garcia-Fernandez M, Lopez-Barneo J: Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4354-9.

However, rotenone, a complex I blocker, selectively occludes the responsiveness to hypoxia of glomus cells in a dose-dependent manner.
6(0,0,1,1) Details
6317663 Kang D, Narabayashi H, Sata T, Takeshige K: Kinetics of superoxide formation by respiratory chain NADH- dehydrogenase of bovine heart mitochondria. Neuroscience. 2007 Mar 2;145(1):130-41. Epub 2007 Jan 4.

Formation of superoxide anions (O2-) by bovine heart NADH-dehydrogenase preparation (Complex I) supported by an NADH- or NADPH-generating system was studied kinetically.
The plots of the NADH-dependent activity of rotenone-treated submitochondrial particles were also biphasic.
3(0,0,0,3) Details
18797987 Martins VP, Soriani FM, Magnani T, Tudella VG, Goldman GH, Curti C, Uyemura SA: Mitochondrial function in the yeast form of the pathogenic fungus Paracoccidioides brasiliensis. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2826-31.

Respiration, membrane potential, and oxidative phosphorylation in mitochondria from P. brasiliensis spheroplasts were evaluated in situ, and the presence of a complete (Complex I-V) functional respiratory chain was demonstrated.
The presence of an alternative NADH-ubiquinone oxidoreductase was indicated by: (i) the ability to oxidize exogenous NADH and (ii) the lack of sensitivity to rotenone and presence of sensitivity to flavone.
3(0,0,0,3) Details
11403652 Galkin AS, Grivennikova VG, Vinogradov AD: H+/2e- stoichiometry of the nadh:ubiquinone reductase reaction catalyzed by submitochondrial particles. Biochim Biophys Acta. 1998 May 6;1364(2):287-96.

Mitochondrial NADH:ubiquinone-reductase (Complex I) catalyzes proton translocation into inside-out submitochondrial particles.
Thus, thermally induced deactivation of Complex I as well as specific inhibitors of the endogenous ubiquinone reduction (rotenone, piericidin A) do not inhibit the proton translocating activity of the enzyme.
2(0,0,0,2) Details
2721632 Davies KP, Zahner H, Kohler P: Litomosoides carinii: mode of action in vitro of benzothiazole and amoscanate derivatives with antifilarial activity. Exp Parasitol. 1989 May;68(4):382-91.

It was confirmed that the drugs CGP 20376, 21835, 20308, 21306, and 6140 cause a rapid immobilization in vitro of the adult filarial worm, Litomosoides carinii, the time required being similar to rotenone at the same concentration.
This effect on SMP respiration could be overcome by using succinate as a substrate, indicating the site of inhibition to be within complex I of the mitochondrial respiratory chain.
2(0,0,0,2) Details
19486265 Hajieva P, Mocko JB, Moosmann B, Behl C: Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity. J Neurochem. 2009 Jul;110(1):118-32. Epub 2009 May 26.

We have employed human dopaminergic neuroblastoma cells and rat primary mesencephalic neurons to assess the protective potential of three novel bisarylimine antioxidants on dopaminergic cell death induced by complex I inhibition or glutathione depletion.
We have found that exceptionally low concentrations (EC (50) values approximately 20 nM) of these compounds (iminostilbene, phenothiazine, and phenoxazine) exhibited strong protective effects against the toxicities of MPP (+), rotenone, and l-buthionine sulfoximine.
1(0,0,0,1) Details
12842875 Lee JM, Shih AY, Murphy TH, Johnson JA: NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. Int J Parasitol. 1995 Jan;25(1):15-21.

Nrf2-/- neurons in this mixed culture system were more sensitive to mitochondrial toxin (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine or rotenone)-induced apoptosis compared with Nrf2+/+ neurons.
1(0,0,0,1) Details
18615648 Schuh RA, Matthews CC, Fishman PS: Interaction of mitochondrial respiratory inhibitors and excitotoxins potentiates cell death in hippocampal slice cultures. J Neurosci Res. 2008 Nov 15;86(15):3306-13.

The broad-spectrum insecticide rotenone, an inhibitor of complex I of the mitochondrial electron transport chain (ETC), gives rise to oxidative stress and bioenergetic failure.
The broad-spectrum insecticide rotenone, an inhibitor of complex I of the mitochondrial electron transport chain (ETC), gives rise to oxidative stress and bioenergetic failure.
1(0,0,0,1) Details
8806593 Guidarelli A, Brambilla L, Cattabeni F, Cantoni O: Pyruvate enhances DNA single-strand break formation while abolishing cytotoxicity in U937 cells exposed to tert-butylhydroperoxide. J Neurochem. 2007 Oct;103(1):131-44.

Rotenone, an inhibitor of complex I, abolished both effects but did not, however, affect the DNA SSB-frequency observed after treatment with tB-OOH alone.
Rotenone, an inhibitor of complex I, abolished both effects but did not, however, affect the DNA SSB-frequency observed after treatment with tB-OOH alone.
1(0,0,0,1) Details
7666176 Marey-Semper I, Gelman M, Levi-Strauss M: A selective toxicity toward cultured mesencephalic dopaminergic neurons is induced by the synergistic effects of energetic metabolism impairment and NMDA receptor activation. Biochem Pharmacol. 2003 Jan 1;65(1):51-7.

In order to demonstrate the existence of such a selective vulnerability, the toxic effects of rotenone, an inhibitor of complex I of the respiratory chain, and of glutamate, which is very likely involved in the neurotoxicity induced by an energetic stress, were analyzed on cultured mouse mesencephalic neurons.
In order to demonstrate the existence of such a selective vulnerability, the toxic effects of rotenone, an inhibitor of complex I of the respiratory chain, and of glutamate, which is very likely involved in the neurotoxicity induced by an energetic stress, were analyzed on cultured mouse mesencephalic neurons.
1(0,0,0,1) Details
16979221 Leiser SF, Salmon AB, Miller RA: Correlated resistance to glucose deprivation and cytotoxic agents in fibroblast cell lines from long-lived pituitary dwarf mice. Planta. 2001 Apr;212(5-6):765-73.

Snell dwarf fibroblasts are here reported to differ from control cell lines in two other respects: they are relatively resistant to the metabolic inhibition induced by low glucose concentrations, and also resistant to the effects of the mitochondrial poison rotenone, a blocker of Complex I of the electron transport chain.
Snell dwarf fibroblasts are here reported to differ from control cell lines in two other respects: they are relatively resistant to the metabolic inhibition induced by low glucose concentrations, and also resistant to the effects of the mitochondrial poison rotenone, a blocker of Complex I of the electron transport chain.
1(0,0,0,1) Details
15560892 Belyaeva EA, Glazunov VV, Korotkov SM: Cd2+ versus Ca2+-produced mitochondrial membrane permeabilization: a proposed direct participation of respiratory complexes I and III. Mech Ageing Dev. 2006 Nov;127(11):821-9. Epub 2006 Sep 18.

A possible involvement of respiratory chain components, namely complex I (P-site) and complex III (S-site) in Cd2+ and/or Ca2+-produced MMP was discussed.
Similarity and distinction in action of rotenone, oligomycin, N-ethylmaleimide, dithiothreitol, catalase, dibucaine, ruthenium red, cyclosporin A (CsA), and ADP on Cd2+ and/or Ca2+-induced mitochondrial dysfunction were revealed.
1(0,0,0,1) Details
15934940 Moon Y, Lee KH, Park JH, Geum D, Kim K: Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. Biochem J. 1997 Dec 15;328 ( Pt 3):801-6.

This action is thought to be relevant to its inhibition of the mitochondrial complex I, but the precise mechanism of this suppression in selective neuronal death is still elusive.
1(0,0,0,1) Details
16531806 Lijnen P, Papparella I, Petrov V, Semplicini A, Fagard R: Angiotensin II-stimulated collagen production in cardiac fibroblasts is mediated by reactive oxygen species. Biochemistry. 1992 Nov 24;31(46):11425-34.

CONCLUSIONS: Our data show that in adult rat cardiac fibroblasts the membrane-associated NAD (P) H oxidase complex is the predominant source of superoxide anion and reactive oxygen species generation in angiotensin II-stimulated adult cardiac fibroblasts.
Rotenone, allopurinol, indomethacin, nordihydroguiaretic acid, ketoconazole and nitro-L-arginine (inhibitors of mitochondrial NAD (P) H oxidase, xanthine oxidase, cyclooxygenase, lipoxygenase, cytochrome P450 oxygenase and nitric oxide synthase, respectively) did not affect the angiotensin II-induced collagen production.
1(0,0,0,1) Details
20151456 Lohrke B, Xu J, Weitzel JM, Kruger B, Goldammer T, Viergutz T: N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction. J Bioenerg Biomembr. 2000 Dec;32(6):609-15.

A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering.
A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering.
1(0,0,0,1) Details
15698934 Wang XJ, Xu JX: Possible involvement of Ca2+ signaling in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem. 2003 Jul;86(1):196-209.

Rotenone, an inhibitor of mitochondrial respiratory chain complex I, is a useful tool to elicit animal model of Parkinson's disease.
1(0,0,0,1) Details
7622333 Armson A, Grubb WB, Mendis AH: Strongyloides ratti: mitochondrial enzyme activities of the classical electron transport pathway in the infective (L3) larvae. Neurotox Res. 2006 Jan;9(1):47-57.

The NCR and NOX activities were 39.3% and 23.5% of the NFR activity, suggesting the occurrence of a rate-limiting step or bifurcation of the respiratory electron transport (RET) pathway on the oxygen-side of RET-Complex I.
Antimycin A and rotenone but not 2-thenoyl trifluoroacetone (TTFA) inhibited NCR activity, the EC50 values were 3.6 x 10 (-6) M, 3.7 x 10 (-7) M, respectively.
1(0,0,0,1) Details
11097871 Gennari A, Viviani B, Galli CL, Marinovich M, Pieters R, Corsini E: Organotins induce apoptosis by disturbance of [Ca (2+)](i) and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes. Blood. 2005 Feb 15;105(4):1717-23. Epub 2004 Oct 14.

ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca (2+) chelator, or rotenone, an inhibitor of the electron entry from complex I to ubiquinone, indicating the important role of Ca (2+) and mitochondria during these early intracellular events.
ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca (2+) chelator, or rotenone, an inhibitor of the electron entry from complex I to ubiquinone, indicating the important role of Ca (2+) and mitochondria during these early intracellular events.
1(0,0,0,1) Details
2827635 Reed JS, Ragan CI: The effect of rate limitation by cytochrome c on the redox state of the ubiquinone pool in reconstituted NADH: cytochrome c reductase. J Cardiovasc Pharmacol. 2008 May;51(5):483-91.

These conditions can be met by reconstituted NADH: cytochrome c reductase (Complex I-III from bovine heart) when electron flow is rate-limited by a low concentration of cytochrome c.
We show that, in such a system, the dependence of activity (varied by inhibition with rotenone) on the steady-state level of quinone reduction is indeed non-linear and very closely accounted for by the theory.
1(0,0,0,1) Details
19120153 Moldzio R, Piskernik C, Radad K, Rausch WD: Rotenone damages striatal organotypic slice culture. Clin Exp Pharmacol Physiol. 2009 Oct;36(10):e57-64. Epub 2009 Jun 8.

Exposure to rotenone results in degeneration of the nigrostriatal pathway through inhibition of complex I.
81(1,1,1,1) Details
16952382 Panesar NS, Chan KW: Evidence for nitrite reductase activity in intact mouse Leydig tumor cells. Free Radic Biol Med. 2008 May 1;44(9):1762-71. Epub 2008 Feb 13.

In stimulated MLTC-1, MRCC inhibitors decreased testosterone production, order being: complex III (antimycin A and myxothiazol) > complex I (rotenone) > complex II (thenoyltrifluoroacetone), while cAMP production increased inversely.
81(1,1,1,1) Details
9350628 Mojet MH, Mills E, Duchen MR: Hypoxia-induced catecholamine secretion in isolated newborn rat adrenal chromaffin cells is mimicked by inhibition of mitochondrial respiration. BMC Neurosci. 2007 Aug 16;8:67.

Inhibition of mitochondrial respiration either by CN- at complex IV or by rotenone at complex I mimicked severe hypoxia, reversibly increasing both [Ca2+] i and catecholamine secretion.
81(1,1,1,1) Details
16034640 Baby SM, Roy A, Lahiri S: Role of mitochondria in the regulation of hypoxia-inducible factor-1alpha in the rat carotid body glomus cells. Methods Enzymol. 2009;456:169-81.

To test this hypothesis in the CB glomus cells, we studied the effect of mitochondrial electron transport chain (ETC) inhibitors: rotenone (complex I; 1 microM), malonate (complex II; 0.5 M), antimycin A (complex III; 1 microg/ml), sodium azide (complex IV; 5 mM), and uncoupler of oxidative phosphorylation: carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP; 1 mM) on HIF-1alpha expression during normoxia and hypoxia.
81(1,1,1,1) Details
12151787 Lehmensiek V, Tan EM, Schwarz J, Storch A: Expression of mutant alpha-synucleins enhances dopamine transporter-mediated MPP+ toxicity in vitro. J Bioenerg Biomembr. 2002 Dec;34(6):413-21.

We demonstrate that expression of all alpha-synuclein isoforms enhances toxicity of general complex I inhibition (rotenone), but only the expression of mutant alpha-synucleins induces significant increased DAT-dependent toxicity of very low concentrations of MPP+ compared to wild-type protein.
81(1,1,1,1) Details
11181577 Petruzzella V, Vergari R, Puzziferri I, Boffoli D, Lamantea E, Zeviani M, Papa S: A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome. J Biol Chem. 2001 Nov 2;276(44):41394-8. Epub 2001 Aug 29.

Fibroblast cultures from the patient exhibited severe reduction of the rotenone-sensitive NADH--> UQ oxidoreductase activity of complex I, which was insensitive to cAMP stimulation.
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9452319 Blandini F, Nappi G, Greenamyre JT: Quantitative study of mitochondrial complex I in platelets of parkinsonian patients. Life Sci. 2009 Aug 12;85(7-8):276-80. Epub 2009 Jun 9.

To obtain quantitative information on platelet complex I in PD, we studied platelet complex I in 16 PD patients and 16 age-matched controls by using a newly developed technique based on the binding of [3H] dihydrorotenone ([3H] DHR), an analog of the pesticide rotenone, to complex I.
35(0,1,1,5) Details
14521988 Lannuzel A, Michel PP, Hoglinger GU, Champy P, Jousset A, Medja F, Lombes A, Darios F, Gleye C, Laurens A, Hocquemiller R, Hirsch EC, Ruberg M: The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism. IUBMB Life. 2004 Aug;56(8):477-82.

The death of dopaminergic neurons induced by systemic administration of mitochondrial respiratory chain complex I inhibitors such as 1-methyl-4-phenylpyridinium (MPP (+); given as the prodrug 1-methyl-1,2,3,6-tetrahydropyridine) or the pesticide rotenone have raised the question as to whether this family of compounds are the cause of some forms of Parkinsonism.
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8512593 Anderson WM, Wood JM, Anderson AC: Inhibition of mitochondrial and Paracoccus denitrificans NADH-ubiquinone reductase by oxacarbocyanine dyes. Toxicol Appl Pharmacol. 2009 Oct 15;240(2):198-207. Epub 2009 Jul 17.

The mechanism of inhibition of the oxacarbocyanines appears to be similar to that of rotenone since (a) essentially only electron acceptors affected by rotenone were affected by the compounds, (b) inhibition of menadione reduction was diminished drastically with rotenone-saturated SMP, and (c) inhibition of coenzyme Q1 was largely eliminated with rotenone-insensitive complex I, and P. denitrificans membrane vesicles.
33(0,1,1,3) Details
18492763 Koppers AJ, De Iuliis GN, Finnie JM, McLaughlin EA, Aitken RJ: Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa. Int J Biol Sci. 2007 Jul 13;3(5):335-41.

RESULTS: Disruption of mitochondrial electron transport flow in human spermatozoa resulted in generation of ROS from complex I (rotenone sensitive) or III (myxothiazol, antimycin A sensitive) via mechanisms that were independent of mitochondrial membrane potential.
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18687689 Selivanov VA, Zeak JA, Roca J, Cascante M, Trucco M, Votyakova TV: The role of external and matrix pH in mitochondrial reactive oxygen species generation. J Bioenerg Biomembr. 2008 Dec;40(6):587-98. Epub 2008 Nov 14.

ROS production increase induced by the alkalization of medium was observed with intact respiring mitochondria as well as in the presence of complex I inhibitor rotenone, which enhanced reactive oxygen species release.
32(0,1,1,2) Details
10486562 Hohler B, Lange B, Holzapfel B, Goldenberg A, Hanze J, Sell A, Testan H, Moller W, Kummer W: Hypoxic upregulation of tyrosine hydroxylase gene expression is paralleled, but not induced, by increased generation of reactive oxygen species in PC12 cells. FEBS Lett. 1999 Aug 20;457(1):53-6.

This increase is abolished by intracellular superoxide scavenging by Mn (III)-tetrakis (1-methyl-4-pyridyl)-porphyrin, and reduced or absent in the presence of the flavoprotein/complex I inhibitors, diphenyl-eneiodonium and rotenone.
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18854758 Nozoe M, Hirooka Y, Koga Y, Araki S, Konno S, Kishi T, Ide T, Sunagawa K: Mitochondria-derived reactive oxygen species mediate sympathoexcitation induced by angiotensin II in the rostral ventrolateral medulla. J Hypertens. 2008 Nov;26(11):2176-84.

Overexpression of Mn-SOD and rotenone, a mitochondrial respiratory complex I inhibitor, suppressed AngII-induced ROS production.
31(0,1,1,1) Details
12358746 Starkov AA, Polster BM, Fiskum G: Regulation of hydrogen peroxide production by brain mitochondria by calcium and Bax. Plant Physiol Biochem. 2005 Jan;43(1):61-7.

In the presence of the respiratory chain Complex I inhibitor rotenone, accumulation of Ca2+ stimulated H2O2 production by mitochondria oxidizing succinate, and this stimulation was associated with release of mitochondrial cytochrome c.
31(0,1,1,1) Details
18801963 Garciarena CD, Caldiz CI, Correa MV, Schinella GR, Mosca SM, Chiappe de Cingolani GE, Cingolani HE, Ennis IL: Na+/H+ exchanger-1 inhibitors decrease myocardial superoxide production via direct mitochondrial action. Mol Aspects Med. 1997;18 Suppl:S263-7.

The mitochondria appeared to be the source of the NOX-dependent ROS released by the "ROS-induced ROS release mechanism" that was blunted by the mitochondrial ATP-sensitive potassium channel blockers 5-hydroxydecanoate and glibenclamide, inhibition of complex I of the electron transport chain with rotenone, and inhibition of the permeability transition pore (MPTP) by cyclosporin A.
31(0,1,1,1) Details
16239214 Ved R, Saha S, Westlund B, Perier C, Burnam L, Sluder A, Hoener M, Rodrigues CM, Alfonso A, Steer C, Liu L, Przedborski S, Wolozin B: Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans. Int J Parasitol. 1995 Feb;25(2):257-60.

C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin.
31(0,1,1,1) Details
1664494 Benzi G, Curti D, Pastoris O, Marzatico F, Villa RF, Dagani F: Sequential damage in mitochondrial complexes by peroxidative stress. Neurosci Lett. 2005 Mar 11;376(2):127-32. Epub 2004 Dec 9.

The cerebral peroxidative stress induces: (a) initially, a decrease in brain GSH concentration concomitant with a decrease in the mitochondrial activity of cytochrome oxidase of aa3-type (complex IV), without changes in ubiquinone and cytochrome b populations; (b) subsequently, an alteration in the transfer molecule cytochrome c and, finally, in rotenone-sensitive NADH-cytochrome c reductase (complex I) and succinate dehydrogenase (complex II).
31(0,1,1,1) Details
15486067 Kim JH, Chu SC, Gramlich JL, Pride YB, Babendreier E, Chauhan D, Salgia R, Podar K, Griffin JD, Sattler M: Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species. Neurochem Res. 1991 Dec;16(12):1295-302.

Elevated ROS levels in BCR-ABL-transformed cells were found to be blocked by the mitochondrial complex I inhibitor rotenone as well as the glucose transport inhibitor phloretin, suggesting that the source of increased ROS might be related to increased glucose metabolism.
31(0,1,1,1) Details
10220277 Konishi K, Tanaka T: Inhibitory effects of tannins on the NADH dehydrogenase activity of bovine heart mitochondrial complex I. Toxicol Appl Pharmacol. 2001 Sep 1;175(2):160-8.

NADH-menadione oxidoreductase activity of complex I was susceptible to the three tannins, but completely resistant to rotenone.
10(0,0,1,5) Details
16963630 Cardol P, Lapaille M, Minet P, Franck F, Matagne RF, Remacle C: ND3 and ND4L subunits of mitochondrial complex I, both nucleus encoded in Chlamydomonas reinhardtii, are required for activity and assembly of the enzyme. Ann Neurol. 1999 Oct;46(4):587-97.

Made of more than 40 subunits, the rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) is the most intricate membrane-bound enzyme of the mitochondrial respiratory chain.
10(0,0,1,5) Details
20224768 Sarafian TA, Montes C, Imura T, Qi J, Coppola G, Geschwind DH, Sofroniew MV: Disruption of astrocyte STAT3 signaling decreases mitochondrial function and increases oxidative stress in vitro. J Exp Biol. 2003 Feb;206(Pt 4):651-8.

Many of the differences observed in STAT3-CKO astrocytes were distinctly altered by exposure to rotenone, suggesting a role for complex I of the mitochondrial electron transport chain.
6(0,0,1,1) Details
1629744 Greenamyre JT, Higgins DS, Eller RV: Quantitative autoradiography of dihydrorotenone binding to complex I of the electron transport chain. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2614-21. Epub 2006 Oct 5.

Unlabeled rotenone and 1-methyl-4-phenylpyridinium ion competed effectively for DHR binding sites.
5(0,0,0,5) Details
11418099 Schuler F, Casida JE: Functional coupling of PSST and ND1 subunits in NADH:ubiquinone oxidoreductase established by photoaffinity labeling. J Biol Chem. 1975 Nov 10;250(21):8472-6.


NADH:ubiquinone oxidoreductase (complex I) is the first, largest and most complicated enzyme of the mitochondrial electron transport chain.
5(0,0,0,5) Details
18763029 Zoccarato F, Cappellotto M, Alexandre A: Clorgyline and other propargylamine derivatives as inhibitors of succinate-dependent H (2) O (2) release at NADH:UBIQUINONE oxidoreductase (Complex I) in brain mitochondria. Bioorg Med Chem Lett. 2003 Nov 17;13(22):4101-5.

O (2)(-) release is low with NAD-linked substrates and increases strongly during succinate oxidation, which increases the QH (2)/Q ratio and is rotenone sensitive.
3(0,0,0,3) Details
1445878 Heinrich H, Werner S: Identification of the ubiquinone-binding site of NADH:ubiquinone oxidoreductase (complex I) from Neurospora crassa. J Neurochem. 2009 Feb;108(4):1045-56.

The activity of the enzyme applying these derivatives is inhibited by 50% at a concentration of 9 and 20 microM rotenone.
3(0,0,0,3) Details
8619621 Schonheit K, Nohl H: Oxidation of cytosolic NADH via complex I of heart mitochondria. . Arch Biochem Biophys. 1996 Mar 15;327(2):319-23.

Our studies exclude both the rotenone-insensitive NADH dehydrogenase of the outer membrane and the endogenous NADH dehydrogenase of damaged mitochondria as being responsible for external NADH consumption.
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17521330 Cermakova P, Verner Z, Man P, Lukes J, Horvath A: Characterization of the NADH:ubiquinone oxidoreductase (complex I) in the trypanosomatid Phytomonas serpens (Kinetoplastida). Biochem Biophys Res Commun. 1996 Sep 4;226(1):70-4.

Spectrophotometric measurement of the NADH:ubiquinone 10 and NADH:ferricyanide dehydrogenase activities revealed their different sensitivities to rotenone, piericidin, and diphenyl iodonium.
2(0,0,0,2) Details
18427623 Levin LA: Mechanisms of retinal ganglion specific-cell death in Leber hereditary optic neuropathy. Neurotox Res. 2008 Dec;14(4):367-82.

RESULTS: The rate of superoxide production in brain mitochondria was more than 5 times the rate in RGC-5 cells when complex I substrates were used.
Rotenone significantly increased the rate of superoxide production in brain but not RGC-5 mitochondria.
1(0,0,0,1) Details
6786284 Takeshige K, Takayanagi R, Minakami S: Lipid peroxidation and the reduction of ADP-Fe3+ chelate by NADH-ubiquinone reductase preparation from bovine heart mitochondria. Biochem J. 1980 Dec 15;192(3):861-6.

The NADH-ubiquinone reductase preparation (Complex I) of bovine hart mitochondria catalysed in the presence of reduced coenzymes and ADP-Fe3+ the lipid peroxidation of liposomes prepared from mitochondrial lipids.
The apparent Km values for the coenzymes and the optimal pH of the reactions agreed well with those of the lipid peroxidation of the submitochondrial particles treated with rotenone.
1(0,0,0,1) Details
16543632 Itoh Y, Takaoka R, Ohira M, Abe T, Tanahashi N, Suzuki N: Reactive oxygen species generated by mitochondrial injury in human brain microvessel endothelial cells. Clin Hemorheol Microcirc. 2006;34(1-2):163-8.

Injury to mitochondrial respiratory chain was induced either with rotenone (an inhibitor of mitochondrial complex I) or with m-chlorocarbonyl cyanide phenylhydrazone (CCCP) (an uncoupler of ATP synthetase).
Injury to mitochondrial respiratory chain was induced either with rotenone (an inhibitor of mitochondrial complex I) or with m-chlorocarbonyl cyanide phenylhydrazone (CCCP) (an uncoupler of ATP synthetase).
1(0,0,0,1) Details
19515065 Dong L, Xie MJ, Zhang P, Ji LL, Liu WC, Dong MQ, Gao F: Rotenone partially reverses decreased BK Ca currents in cerebral artery smooth muscle cells from streptozotocin-induced diabetic mice. Biochim Biophys Acta. 2001 Jul 2;1506(1):79-87.

Control and diabetic mice were treated with 12.7 micromol/L rotenone, an inhibitor of the mitochondrial electron transport chain complex I, or placebo every other day for 5 weeks.
1(0,0,0,1) Details
9878636 Duby F, Matagne RF: Alteration of dark respiration and reduction of phototrophic growth in a mitochondrial DNA deletion mutant of Chlamydomonas lacking cob, nd4, and the 3' end of nd5. Hum Mol Genet. 2001 Mar 1;10(5):529-35.

Due to these mitochondrial DNA alterations, complex I activity, the cytochrome pathway of respiration, and presumably, the three phosphorylation sites associated with these enzyme activities are lacking in the mutant.
The low respiratory rate of the dum24 cells results from the activities of rotenone-resistant NADH dehydrogenase, complex II, and alternative oxidase, with none of these enzymes being coupled to ATP production.
1(0,0,0,1) Details
16624679 Rizzardini M, Lupi M, Mangolini A, Babetto E, Ubezio P, Cantoni L: Neurodegeneration induced by complex I inhibition in a cellular model of familial amyotrophic lateral sclerosis. Plant Cell. 1999 Jan;11(1):115-25.

G93A Cu/Zn superoxide dismutase (SOD1), a human mutant SOD1 associated with familial amyotrophic lateral sclerosis, increased the toxicity of the mitochondrial toxin rotenone in the NSC-34 motoneuronal cell line.
1(0,0,0,1) Details
14592541 Tudella VG, Curti C, Soriani FM, Santos AC, Uyemura SA: In situ evidence of an alternative oxidase and an uncoupling protein in the respiratory chain of Aspergillus fumigatus. Mov Disord. 1998 Jan;13(1):11-5.

Firstly, a functional respiratory chain (complex I-V) was demonstrated: adenosine 5'-diphosphate (ADP) induced an oligomycin-sensitive transition from resting to phophorylating respiration in the presence of the oxidizable substrates malate, glutamate, alpha-ketoglutarate, pyruvate, dihydroorotate, succinate, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and exogenous NADH.
In addition, the ability of the fungus to oxidize exogenous NADH, as well as the insensitivity of its respiration to rotenone, in association with the sensitivity to flavone, indicate the presence of an alternative NADH-ubiquinone oxidoreductase; the partial sensitivity of respiration to antimycin A and cyanide, in association with the sensitivity to benzohydroxamic acid, indicates the presence of an alternative oxidase.
1(0,0,0,1) Details
9603924 Barrientos A, Kenyon L, Moraes CT: Human xenomitochondrial cybrids. J Biol Chem. 2009 Jan 23;284(4):2045-52. Epub 2008 Dec 1.

Kinetic studies of complex I using decylubiquinone or NADH as limiting substrates showed that the Vmax was decreased in HXC by approximately 40%, and the Km for the NADH was significantly increased (3-fold, p < 0.001).
Rotenone inhibition studies of intact cell respiration and pyruvate-malate oxidation in permeabilized cells showed that 3 nM rotenone produced a mild effect in control cells (0-10% inhibition) but produced a marked inhibition of HXC respiration (50-75%).
1(0,0,0,1) Details
12176058 Young TA, Cunningham CC, Bailey SM: Reactive oxygen species production by the mitochondrial respiratory chain in isolated rat hepatocytes and liver mitochondria: studies using myxothiazol. Neuroscience. 2010 Jan 20;165(2):455-62. Epub .

Coincubation with antimycin or rotenone had no effect on myxothiazol-induced ROS levels.
Furthermore, diphenyliodonium, an inhibitor that blocks electron flow through the flavin mononucleotide of mitochondrial complex I and other flavoenzymes, significantly attenuated the myxothiazol-induced increase in hepatocyte ROS levels.
1(0,0,0,1) Details
12853461 Pelicano H, Feng L, Zhou Y, Carew JS, Hileman EO, Plunkett W, Keating MJ, Huang P: Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism. PLoS One. 2009;4(1):e4160. Epub 2009 Jan 8.

This strategy was first tested in a proof-of-principle study using rotenone, a specific inhibitor of mitochondrial electron transport complex I.
81(1,1,1,1) Details
18599602 Watabe M, Nakaki T: Mitochondrial complex I inhibitor rotenone inhibits and redistributes vesicular monoamine transporter 2 via nitration in human dopaminergic SH-SY5Y cells. Mol Pharmacol. 2008 Oct;74(4):933-40. Epub 2008 Jul 3.

Long-term systemic mitochondrial complex I inhibition by rotenone induces selective degeneration of dopaminergic neurons in rats.
81(1,1,1,1) Details
10841308 de Halac IN, Bacman SR, de Kremer RD: Histoenzymology of oxidases and dehydrogenases in peripheral blood lymphocytes and monocytes for the study of mitochondrial oxidative phosphorylation. Toxicol Sci. 2007 Jan;95(1):196-204. Epub 2006 Oct 12.

Complex I activity was detected, but inhibition with rotenone was incomplete.
81(1,1,1,1) Details
15924876 Li J, French BA, Nan L, Fu P, French SW: Uncoupling of oxidative phosphorylation prevents the urinary alcohol level cycling caused by feeding ethanol continuously at a constant rate. Anal Biochem. 2003 Feb 1;313(1):46-52.

The question was: is the rate of oxidative phosphorylation fluxuation essential for the cycle to occur? The question has been partially answered by showing that rotenone, which inhibits complex I, blocks the cycle by preventing the generation of NAD from NADH.
81(1,1,1,1) Details
1445939 Kotlyar AB, Gutman M: The effect of delta mu H+ on the interaction of rotenone with complex I of submitochondrial particles. Mol Pharmacol. 1998 Jun;53(6):1076-82.
81(1,1,1,1) Details
16412576 Chen MJ, Yap YW, Choy MS, Koh CH, Seet SJ, Duan W, Whiteman M, Cheung NS: Early induction of calpains in rotenone-mediated neuronal apoptosis. Biochim Biophys Acta. 1992 Dec 7;1140(2):169-74.

Rotenone is an inhibitor of mitochondrial complex I that produces a model of Parkinson's disease (PD), where neurons undergo apoptosis by caspase-dependent and/or caspase-independent pathways.
81(1,1,1,1) Details
10982813 Seo BB, Wang J, Flotte TR, Yagi T, Matsuno-Yagi A: Use of the NADH-quinone oxidoreductase (NDI1) gene of Saccharomyces cerevisiae as a possible cure for complex I defects in human cells. Brain Res Bull. 2006 Apr 28;69(4):465-74. Epub 2006 Mar 10.

Furthermore, when cells were cultured under the conditions where energy has to be provided by respiration, the NDI1-transduced cells were able to grow even in the presence of added complex I inhibitor such as rotenone and 1-methyl-4-phenylpyridinium ion.
35(0,1,1,5) Details
16581014 Yagi T, Seo BB, Nakamaru-Ogiso E, Marella M, Barber-Singh J, Yamashita T, Matsuno-Yagi A: Possibility of transkingdom gene therapy for complex I diseases. Brain Res Bull. 2007 Mar 30;71(6):633-40. Epub 2007 Jan 8.

The NDI1-transduced cells were more resistant to complex I inhibitors and diminished production of reactive oxygen species induced by rotenone.
35(0,1,1,5) Details
15228597 Gyulkhandanyan AV, Pennefather PS: Shift in the localization of sites of hydrogen peroxide production in brain mitochondria by mitochondrial stress. Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1401-7. Epub 2005 Apr 21.

H (2) O (2) production supported by succinate during reverse transfer of electrons was decreased by inhibitors of complex I (rotenone and diphenyleneiodonium) whereas in glutamate/malate-oxidizing mitochondria diphenyleneiodonium decreased while rotenone increased H (2) O (2) generation.
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9989245 Cassarino DS, Parks JK, Parker WD Jr, Bennett JP Jr: The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism. Biol Pharm Bull. 2003 May;26(5):729-32.

Rotenone, a classic non-competitive complex I inhibitor, completely inhibited MPP (+)-induced swelling and release of cytochrome c.
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17292807 Kim YJ, Ko HH, Han ES, Lee CS: Lamotrigine inhibition of rotenone- or 1-methyl-4-phenylpyridinium-induced mitochondrial damage and cell death. J Neurosci Res. 2004 May 15;76(4):563-71.

The aim of the present study was to assess the effect of antiepileptic lamotrigine against the cytotoxicity of mitochondrial respiratory complex I inhibitors rotenone and 1-methyl-4-phenylpyridinium (MPP+) in relation to the mitochondria-mediated cell death process and oxidative stress.
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15540952 Caboni P, Sherer TB, Zhang N, Taylor G, Na HM, Greenamyre JT, Casida JE: Rotenone, deguelin, their metabolites, and the rat model of Parkinson's disease. J Immunol. 2006 Jul 15;177(2):852-62.

We previously established that the hydroxylated metabolites and derivatives of rotenone and deguelin are all less active (i.e., detoxified) as complex I inhibitors relative to the parent rotenoids.
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14505934 Deng Y, Nicholson RA: Stimulation by surangin B of endogenous amino acid release from synaptosomes. Basic Clin Pharmacol Toxicol. 2010 Jan;106(1):53-61. Epub 2009 Oct 28.

Rotenone (a complex I inhibitor) and carbonyl cyanide chlorophenylhydrazone (CCCP; an uncoupler), were more potent releasers of amino acids from synaptosomes than surangin B, however, carboxin (a complex II-selective inhibitor), was extremely weak to ineffective in this regard.
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19885011 Kim HJ, Song JY, Park HJ, Park HK, Yun DH, Chung JH: Naringin Protects against Rotenone-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells. Korean J Physiol Pharmacol. 2009 Aug;13(4):281-5. Epub 2009 Aug 31.

Rotenone, a mitochondrial complex I inhibitor, can induce the pathological features of Parkinson's disease (PD).
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19741132 Ng CH, Mok SZ, Koh C, Ouyang X, Fivaz ML, Tan EK, Dawson VL, Dawson TM, Yu F, Lim KL: Parkin protects against LRRK2 G2019S mutant-induced dopaminergic neurodegeneration in Drosophila. J Biol Chem. 2002 Nov 22;277(47):44784-90. Epub 2002 Sep 16.

Furthermore, LRRK2 mutant flies also display reduced lifespan and increased sensitivity to rotenone, a mitochondrial complex I inhibitor.
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15910763 Grammatopoulos TN, Ahmadi F, Jones SM, Fariss MW, Weyhenmeyer JA, Zawada WM: Angiotensin II protects cultured midbrain dopaminergic neurons against rotenone-induced cell death. Brain Res. 2005 May 31;1045(1-2):64-71. Epub 2005 Apr 26.

Primary ventral mesencephalic (VM) cultures from E15 rats were grown for 5 days and then cultured in the presence of the mitochondrial complex I inhibitor, rotenone.
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16378625 Wu CC, Hsu MC, Hsieh CW, Lin JB, Lai PH, Wung BS: Upregulation of heme oxygenase-1 by Epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. J Bioenerg Biomembr. 2002 Jun;34(3):193-208.

The inhibition of intracellular ROS production by N-acetylcysteine (NAC), glutathione (GSH), superoxide dismutase (SOD), catalase and the mitochondrial complex I inhibitor, rotenone, results in a decrease in EGCG-dependent HO-1 expression.
31(0,1,1,1) Details
18353897 Koopman WJ, Distelmaier F, Hink MA, Verkaart S, Wijers M, Fransen J, Smeitink JA, Willems PH: Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria. J Biol Chem. 1988 Nov 25;263(33):17566-75.

We demonstrated previously that inhibition of mitochondrial complex I (CI or NADH:ubiquinone oxidoreductase) by rotenone accelerated matrix protein diffusion and decreased the fraction and velocity of moving mitochondria.
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15545227 Scatena R, Martorana GE, Bottoni P, Giardina B: Mitochondrial dysfunction by synthetic ligands of peroxisome proliferator activated receptors (PPARs). Exp Toxicol Pathol. 1993 Oct;45(5-6):375-80.

A re-evaluation of the biological activities of PPAR synthetic ligands, in particular of the mitochondrial dysfunction based on a rotenone-like Complex I partial inhibition and of its consequent metabolic adaptations, seems to explain some of the pathophysiologic aspects of PPARs allowing a better definition of the therapeutic properties of the so-called PPAR-ligands.
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19857556 Li X, Liu Z, Tamashiro K, Shi B, Rudnicki DD, Ross CA, Moran TH, Smith WW: Synphilin-1 exhibits trophic and protective effects against Rotenone toxicity. Toxicol Appl Pharmacol. 2000 Dec 1;169(2):185-90.

Rotenone, mitochondrial complex I inhibitor, has been shown previously to induce dopaminergic neurodegeneration and Parkinsonism in rats and Drosophila.
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19409896 Greene JG, Noorian AR, Srinivasan S: Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson's disease. Arch Biochem Biophys. 2002 Sep 1;405(1):65-72.

We report that the parkinsonian neurotoxin and mitochondrial complex I inhibitor rotenone causes delayed gastric emptying and enteric neuronal dysfunction when administered chronically to rats in the absence of major motor dysfunction or CNS pathology.
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7632092 Campos Y, Arenas J, Cabello A, Gomez-Reino JJ: Respiratory chain enzyme defects in patients with idiopathic inflammatory myopathy. Stem Cells. 2008 Jan;26(1):64-71. Epub 2007 Oct 18.

Activity of rotenone sensitive NADH cytochrome c reductase (complex I and III) succinate dehydrogenase (complex II), succinate cytochrome c reductase (complex II and III), cytochrome c oxidase (complex IV), and citrate synthase (a mitochondrial matrix enzyme), was measured spectrophotometrically in muscle homogenates.
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19854245 Brawek B, Loffler M, Wagner K, Huppertz HJ, Wendling AS, Weyerbrock A, Jackisch R, Feuerstein TJ: Reactive oxygen species (ROS) in the human neocortex: role of aging and cognition. Brain Res. 2005 Jul 12;1049(2):147-55.

The increase in the concentration-response curve of the complex I inhibitor rotenone on ROS generation, as measured by rhodamine 123 (Rh123) fluorescence, was much more pronounced than that of rotenone on mitochondrial [(3) H]-choline uptake [which indicates changes in the mitochondrial membrane potential (DeltaPsi (M))].
31(0,1,1,1) Details
14740892 Pasdois P, Deveaud C, Voisin P, Bouchaud V, Rigoulet M, Beauvoit B: Contribution of the phosphorylable complex I in the growth phase-dependent respiration of C6 glioma cells in vitro. Biochem J. 2004 May 15;380(Pt 1):193-202.

Nevertheless, a quantitative correlation was found between cellular respiration and the rotenone-sensitive NADH ubiquinone oxidoreductase (i.e. complex I) activity.
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11695835 Chomyn A: Mitochondrial genetic control of assembly and function of complex I in mammalian cells. Circ Res. 2003 Sep 19;93(6):573-80. Epub 2003 Aug 14.

Subsequently, we isolated several mutants affected in one or another of the mtDNA-encoded subunits of complex I by exposing established cell lines to high concentrations of rotenone.
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19961238 Shinzawa-Itoh K, Seiyama J, Terada H, Nakatsubo R, Naoki K, Nakashima Y, Yoshikawa S: Bovine heart NADH-ubiquinone oxidoreductase contains one molecule of ubiquinone with ten isoprene units as one of the cofactors. J Biol Chem. 2005 Nov 25;280(47):39033-41. Epub 2005 Sep 26.

The rotenone-sensitive enzymatic activity of the Complex I preparation was comparable to that of Complex I in the mitochondrial membrane.
9(0,0,1,4) Details
19280713 Chinta SJ, Rane A, Yadava N, Andersen JK, Nicholls DG, Polster BM: Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria. Free Radic Biol Med. 2009 Apr 1;46(7):939-47.

Isolated Hq brain mitochondria oxidizing complex I substrates displayed no difference compared to wild type (WT) in basal ROS production, H2O2 removal, or ROS production stimulated by complex I inhibitors rotenone or 1-methyl-4-phenylpyridinium.
5(0,0,0,5) Details
7948420 Maklashina EO, Sled' VD, Vinogradov AD: [Hysteresis behavior of complex I from bovine heart mitochondria: kinetic and thermodynamic parameters of retarded reverse transition from the inactive to active state]. Biokhimiia. 1994 Jul;59(7):946-57.

The active form catalyzes the rapid rotenone-sensitive, N-ethylmaleimide-insensitive NADH : Q1 reductase reaction.
5(0,0,0,5) Details
8026508 De Jong AM, Albracht SP: Ubisemiquinones as obligatory intermediates in the electron transfer from NADH to ubiquinone. Plant Mol Biol. 1992 Dec;20(6):1097-110.

Until now ubisemiquinones associated with NADH:ubiquinone oxidoreductase (complex I) have been reported to occur in isolated enzyme and in tightly coupled submitochondrial particles.
The EPR signal of the rotenone-sensitive ubisemiquinones could be detected not only in coupled MgATP submitochondrial particles, but also in routine preparations of uncoupled submitochondrial particles and in mitochondria.
3(0,0,0,3) Details
19526285 Mallajosyula JK, Chinta SJ, Rajagopalan S, Nicholls DG, Andersen JK: Metabolic control analysis in a cellular model of elevated MAO-B: relevance to Parkinson's disease. J Biol Chem. 2000 Dec 1;275(48):37774-8.


MAO-B mediated increases in H (2) O (2) also appeared to result in direct oxidative inhibition of both mitochondrial complex I and aconitase.
3(0,0,0,3) Details
18182110 Hoegger MJ, Lieven CJ, Levin LA: Differential production of superoxide by neuronal mitochondria. . J Clin Endocrinol Metab. 2010 Feb;95(2):894-902. Epub 2009 Dec 18.

For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs), a central neuron contained within the retina.
Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A.
3(0,0,0,3) Details
386 Ragan CI, Hinkle PC: Ion transport and respiratory control in vesicles formed from reduced nicotinamide adenine dinucleotide coenzyme Q reductase and phospholipids. Mol Biochem Parasitol. 2002 Aug 28;123(2):135-42.


NADH-coenzyme Q reductase from bovine heart mitochondria (complex I) was incorporated into phospholipid vesicles by the cholate dialysis procedure.
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11311802 Dedov VN, Mandadi S, Armati PJ, Verkhratsky A: Capsaicin-induced depolarisation of mitochondria in dorsal root ganglion neurons is enhanced by vanilloid receptors. Neuroscience. 2001;103(1):219-26.

Rotenone, an inhibitor of complex I of the mitochondrial respiratory chain, and oligomycin, an inhibitor of F (0) F (1)-ATPase, significantly enhanced the mitochondrial depolarisation produced by capsaicin in DRG neurons.
Rotenone, an inhibitor of complex I of the mitochondrial respiratory chain, and oligomycin, an inhibitor of F (0) F (1)-ATPase, significantly enhanced the mitochondrial depolarisation produced by capsaicin in DRG neurons.
2(0,0,0,2) Details
17289351 Verkaart S, Koopman WJ, van Emst-de Vries SE, Nijtmans LG, van den Heuvel LW, Smeitink JA, Willems PH: Superoxide production is inversely related to complex I activity in inherited complex I deficiency. Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):660-5. Epub 2008 Apr 30.

In agreement with this finding, rotenone, a potent inhibitor of CI activity, dose-dependently increased superoxide production in healthy control cells.
2(0,0,0,2) Details
9588024 Matsuo M, Endo T, Asada K: Properties of the respiratory NAD (P) H dehydrogenase isolated from the cyanobacterium Synechocystis PCC6803. Plant Cell Physiol. 1998 Mar;39(3):263-7.

The enzymatic activity was inhibited by diphenyleneiodonium chloride and salicylhydroxamic acid, but not by rotenone, p-chloromercuribenzoate, N-ethylmaleimide, flavon, dicumarol, or antimycin A.
These results suggest that the purified complex is a hydrophilic subcomplex which contains an NADPH binding site and flavin, and is dissociated from a hydrophobic subcomplex, which contains quinone binding site.
1(0,0,0,1) Details
12062413 Svensson AS, Johansson FI, Moller IM, Rasmusson AG: Cold stress decreases the capacity for respiratory NADH oxidation in potato leaves. FEBS Lett. 2002 Apr 24;517(1-3):79-82.

The nda1 and ndb1 genes, homologues to genes encoding the non-proton-pumping respiratory chain NADH dehydrogenases of Escherichia coli and yeast, were compared to genes encoding catalytic subunits of the proton-pumping NADH dehydrogenase (complex I).
This decrease is accompanied by specific decreases of immunodetected NDA protein and internal rotenone-insensitive NADH oxidation in mitochondria isolated from cold-treated plants.
1(0,0,0,1) Details
11566731 Vernet P, Fulton N, Wallace C, Aitken RJ: Analysis of reactive oxygen species generating systems in rat epididymal spermatozoa. Biol Reprod. 2001 Oct;65(4):1102-13.

Reverse transcription-polymerase chain reaction analysis indicated that the sperm NAD (P) H oxidoreductase complex is quite distinct from the equivalent leukocyte system.
This increase could be blocked by rotenone and oligomycin (R/O) in the presence of malate or lactate but not succinate.
1(0,0,0,1) Details
19807658 Choi K, Kim J, Kim GW, Choi C: Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species. Neurotox Res. 2009 Oct;16(3):186-93. Epub 2009 Mar 5.

The inhibition of mitochondrial hyperpolarization by diphenylene iodonium or rotenone, potent inhibitors of mitochondrial respiratory chain complex I, resulted in reduced ROS production and subsequent neuronal cell death in vitro and in vivo.
The inhibition of mitochondrial hyperpolarization by diphenylene iodonium or rotenone, potent inhibitors of mitochondrial respiratory chain complex I, resulted in reduced ROS production and subsequent neuronal cell death in vitro and in vivo.
1(0,0,0,1) Details
7904221 Marey-Semper I, Gelman M, Levi-Strauss M: The high sensitivity to rotenone of striatal dopamine uptake suggests the existence of a constitutive metabolic deficiency in dopaminergic neurons from the substantia nigra. Curr Neurovasc Res. 2009 Nov;6(4):213-22.

The toxicity of the 1-methyl-4-phenylpyridinium ion (MPP+), an inhibitor of complex I of the respiratory chain, on nigrostriatal dopaminergic neurons contrasts with its relative inefficiency towards other catecholaminergic cell populations in spite of their ability to accumulate this neurotoxin through their high-affinity uptake system.
1(0,0,0,1) Details
9092484 Miyako K, Kai Y, Irie T, Takeshige K, Kang D: The content of intracellular mitochondrial DNA is decreased by 1-methyl-4-phenylpyridinium ion (MPP+). Neuroscience. 2008 Mar 3;152(1):198-207.

On the contrary, 0.1 microM rotenone, which inhibits complex I to the same extent as 25 microM MPP+ in the cells, increases the content of mitochondrial DNA about 2-fold.
82(1,1,1,2) Details
12724545 Dutilleul C, Garmier M, Noctor G, Mathieu C, Chetrit P, Foyer CH, de Paepe R: Leaf mitochondria modulate whole cell redox homeostasis, set antioxidant capacity, and determine stress resistance through altered signaling and diurnal regulation. J Biol Chem. 2005 Dec 23;280(51):42026-35. Epub 2005 Oct 21.

The cytoplasmic male-sterile mutant (CMSII) is impaired in complex I function and displays enhanced nonphosphorylating rotenone-insensitive [NAD (P) H dehydrogenases] and cyanide-insensitive (alternative oxidase) respiration.
82(1,1,1,2) Details
16115015 Sousa SC, Castilho RF: Protective effect of melatonin on rotenone plus Ca2+-induced mitochondrial oxidative stress and PC12 cell death. J Neurochem. 2003 Sep;86(5):1297-307.

Chronic systemic inhibition of mitochondrial respiratory chain complex I by rotenone causes nigrostriatal dopaminergic degeneration in rats, producing an in vivo experimental model of Parkinson's disease.
82(1,1,1,2) Details
9379714 Herrero A, Barja G: Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon. Biochemistry. 2007 May 29;46(21):6409-16. Epub 2007 May 3.

This suggests that the free radical generator of Complex I is located after the ferricyanide reduction site, between the ethoxyformic and the rotenone-sensitive sites.
81(1,1,1,1) Details
15850589 Rizzardini M, Mangolini A, Lupi M, Ubezio P, Bendotti C, Cantoni L: Low levels of ALS-linked Cu/Zn superoxide dismutase increase the production of reactive oxygen species and cause mitochondrial damage and death in motor neuron-like cells. Neuroreport. 2004 Oct 5;15(14):2227-31.

The mutant protein rendered G93ASOD1 cells more sensitive to mitochondrial dysfunction induced by stimuli that alter cellular free radical homeostasis, like serum withdrawal, depletion of glutathione by ethacrynic acid or rotenone-mediated inhibition of complex I of the mitochondrial electron transport chain.
81(1,1,1,1) Details
16678116 Chernyak BV, Izyumov DS, Lyamzaev KG, Pashkovskaya AA, Pletjushkina OY, Antonenko YN, Sakharov DV, Wirtz KW, Skulachev VP: Production of reactive oxygen species in mitochondria of HeLa cells under oxidative stress. Mol Neurodegener. 2008 Dec 29;3:21.

In living cells, MR-mediated PDT initiates a delayed ("dark") accumulation of ROS, which is accelerated by inhibitors of the respiratory chain (piericidin, rotenone and myxothiazol) and inhibited by MitoQ and diphenyleneiodonium (an inhibitor of flavin enzymes), indicating that flavin of Complex I is involved in the ROS production.
81(1,1,1,1) Details
15710606 Zoccarato F, Toscano P, Alexandre A: Dopamine-derived dopaminochrome promotes H (2) O (2) release at mitochondrial complex I: stimulation by rotenone, control by Ca (2+), and relevance to Parkinson disease. FEBS Lett. 1991 Nov 4;292(1-2):289-92.

Inhibitors of Complex I of the mitochondrial respiratory chain, such as rotenone, promote Parkinson disease-like symptoms and signs of oxidative stress.
69(0,2,3,4) Details
8595975 Soole KL, Menz RI: Functional molecular aspects of the NADH dehydrogenases of plant mitochondria. J Cereb Blood Flow Metab. 1997 Mar;17(3):265-72.

As well as complex I, plant mitochondria contain several type-II NAD (P) H dehydrogenases which mediate rotenone-insensitive oxidation of cytosolic and matrix NADH.
35(0,1,1,5) Details
10417649 Krebs W, Steuber J, Gemperli AC, Dimroth P: Na+ translocation by the NADH:ubiquinone oxidoreductase (complex I) from Klebsiella pneumoniae. Nutr Metab Cardiovasc Dis. 2010 Mar 12.

The uptake of sodium ions was severely inhibited by the complex I-specific inhibitor rotenone with deaminoNADH or NADH as substrate.
35(0,1,1,5) Details
8585613 Blandini F, Greenamyre JT: Assay of [3H] dihydrorotenone binding to complex I in intact human platelets. J Neurosci. 2004 Sep 8;24(36):7779-88.

We have developed an assay for the binding of [3H]-dihydrorotenone ([3H] DHR), an analogue of the pesticide rotenone, to the mitochondrial enzyme, complex I, in intact human platelets.
33(0,1,1,3) Details
11080300 Sabar M, De Paepe R, de Kouchkovsky Y: Complex I impairment, respiratory compensations, and photosynthetic decrease in nuclear and mitochondrial male sterile mutants of Nicotiana sylvestris. Ann Rheum Dis. 1995 Jun;54(6):491-3.

We have previously shown that in Nicotiana sylvestris cytoplasmic male-sterile (CMS) mutants where the mtDNA lacks the nad7 gene coding for a subunit of respiratory Complex I (NADH:ubiquinone oxidoreductase, EC 1.6.5.3), glycine (Gly) oxidation was lower than in the wild type and insensitive to rotenone, suggesting Complex I dysfunction.
33(0,1,1,3) Details
10989660 Greenamyre JT, MacKenzie G, Peng TI, Stephans SE: Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta. 2007 Sep;1772(9):1041-51. Epub 2007 May 25.

We developed a novel model of PD in which chronic, systemic infusion of rotenone, a complex-I inhibitor, selectively kills dopaminergic nerve terminals and causes retrograde degeneration of substantia nigra neurons over a period of months.
32(0,1,1,2) Details
15890007 Dukes AA, Korwek KM, Hastings TG: The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells. Biochim Biophys Acta. 2010 Apr;1797(4):509-515. Epub 2010 Jan 25.

Systemic exposure to rotenone, a Complex I inhibitor, has been shown to lead to selective dopaminergic cell death in vivo and toxicity in many in vitro models, including dopaminergic cell cultures.
32(0,1,1,2) Details
17041725 Liu YY, Zhao HY, Zhao CL, Duan CL, Lu LL, Yang H: [Overexpression of alpha-synuclein in SH-SY5Y cells partially protected against oxidative stress induced by rotenone]. Stroke. 1996 Feb;27(2):327-31; discussion 332.

After treatment with rotenone, both cell viability and complex I activity in these cells were reduced in a concentration-dependent manner.
32(0,1,1,2) Details
19889626 Olson ML, Chalmers S, McCarron JG: Mitochondrial Ca2+ uptake increases Ca2+ release from inositol 1,4,5-trisphosphate receptor clusters in smooth muscle cells. PLoS One. 2009 May 27;4(5):e5701.

The protonophore carbonyl cyanide 3-chloropheylhydrazone and complex I inhibitor rotenone each depolarized DeltaPsi (M) to prevent mitochondrial Ca2+ uptake and attenuated Ca2+ puffs by approximately 66 or approximately 60%, respectively.
31(0,1,1,1) Details
18562315 Sugeno N, Takeda A, Hasegawa T, Kobayashi M, Kikuchi A, Mori F, Wakabayashi K, Itoyama Y: Serine 129 phosphorylation of alpha-synuclein induces unfolded protein response-mediated cell death. Ann N Y Acad Sci. 2008 Dec;1148:530-5.

Following the treatment with rotenone, a mitochondrial complex I inhibitor, wild type alpha-synuclein-overexpressing cells demonstrated intracellular aggregations, which shared a number of features with Lewy bodies, although cells overexpressing the S129A mutant, in which phosphorylation at Ser (129) was blocked, showed few aggregations.
31(0,1,1,1) Details
8720174 Santhamma KR, Bhaduri A: Characterization of the respiratory chain of Leishmania donovani promastigotes. FEBS Lett. 2003 Aug 28;550(1-3):163-7.

Inhibition analysis of respiration of Leishmania donovani promastigotes in resting, starved and permeabilized cells in the presence of classical electron transfer complex inhibitors such as rotenone, thenoyltrifluoroacetone and antimycin demonstrated the absence of complex I component of the respiratory chain in this organism.
31(0,1,1,1) Details
18832013 Kim HY, Chung JM, Chung K: Increased production of mitochondrial superoxide in the spinal cord induces pain behaviors in mice: the effect of mitochondrial electron transport complex inhibitors. Exp Mol Pathol. 2004 Dec;77(3):210-3.

The levels of mechanical hyperalgesia after antimycin A, a complex III inhibitor, were higher than that with rotenone, a complex I inhibitor.
31(0,1,1,1) Details
16990510 Chen Q, Moghaddas S, Hoppel CL, Lesnefsky EJ: Reversible blockade of electron transport during ischemia protects mitochondria and decreases myocardial injury following reperfusion. Mol Biochem Parasitol. 1995 Dec;75(1):43-53.

The reversible blockade of electron transport during ischemia with amobarbital, an inhibitor at the rotenone site of complex I, protects mitochondria against ischemic damage.
31(0,1,1,1) Details
14580324 Zuo L, Pasniciuc S, Wright VP, Merola AJ, Clanton TL: Sources for superoxide release: lessons from blockade of electron transport, NADPH oxidase, and anion channels in diaphragm. Brain Res. 1997 Apr 4;753(1):157-62.

The mitochondria within intact rat diaphragm were inhibited at complex I (amobarbital or rotenone) or complex I and II (rotenone plus thenoyltrifluoroacetone).
31(0,1,1,1) Details
14697328 Bonsi P, Calabresi P, De Persis C, Papa M, Centonze D, Bernardi G, Pisani A: Early ionic and membrane potential changes caused by the pesticide rotenone in striatal cholinergic interneurons. Antioxid Redox Signal. 2003 Oct;5(5):667-75.

Acute application of the mitochondrial complex I inhibitor rotenone produced an early membrane hyperpolarization coupled to a fall in input resistance, followed by a late depolarizing response.
31(0,1,1,1) Details
7988736 Bereznowski Z: Effect of methyl methacrylate on mitochondrial function and structure. Eur J Biochem. 1996 Oct 1;241(1):280-5.

The data presented suggest that in the isolated mitochondria MM inhibits NADH oxidation in the vicinity of the rotenone sensitive site of complex I. 7.
31(0,1,1,1) Details
11454754 Remacle C, Baurain D, Cardol P, Matagne RF: Mutants of Chlamydomonas reinhardtii deficient in mitochondrial complex I: characterization of two mutations affecting the nd1 coding sequence. Plant Physiol. 2009 Jul;150(3):1286-96. Epub 2009 May 29.

The mitochondrial rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) comprises more than 30 subunits, the majority of which are encoded by the nucleus.
9(0,0,1,4) Details
8761491 Buchanan SK, Walker JE: Large-scale chromatographic purification of F1F0-ATPase and complex I from bovine heart mitochondria. J Neural Transm. 2009 Jul;116(7):791-806. Epub 2009 Jun 6.

The complex I preparation contains all of the subunits identified in other preparations of the enzyme, and has rotenone-sensitive NADH:ubiquinone oxidoreductase and NADH:ferricyanide oxidoreductase activities.
9(0,0,1,4) Details
9711297 Miyoshi H, Ohshima M, Shimada H, Akagi T, Iwamura H, McLaughlin JL: Essential structural factors of annonaceous acetogenins as potent inhibitors of mitochondrial complex I. Biochim Biophys Acta. 2007 Mar;1772(3):373-81. Epub 2007 Jan 4.

These inhibitors act, at the terminal electron transfer step of the enzyme, in a similar way to the usual complex I inhibitors, such as piericidin A and rotenone; however, structural similarities are not apparent between the acetogenins and these known complex I inhibitors.
5(0,0,0,5) Details
17760425 Grivennikova VG, Kotlyar AB, Karliner JS, Cecchini G, Vinogradov AD: Redox-dependent change of nucleotide affinity to the active site of the mammalian complex I. Eur J Biochem. 2002 Aug;269(16):4020-4.

The effect of succinate is completely reversed by rotenone, antimycin A, and uncoupler.
5(0,0,0,5) Details
18037377 Gostimskaya IS, Grivennikova VG, Cecchini G, Vinogradov AD: Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I). Osteoarthritis Cartilage. 2006 Oct;14(10):1011-22. Epub 2006 May 5.

The catalytic activities of the enzyme, i.e. rotenone-insensitive NADH:hexaammineruthenium III reductase and rotenone-sensitive NADH:quinone reductase decline when bovine heart submitochondrial particles are incubated with NADH in the presence of rotenone or cyanide at alkaline pH.
3(0,0,0,3) Details
9266534 Ghelli A, Degli Esposti M, Carelli V, Lenaz G: Changes in mitochondrial complex I activity and coenzyme Q binding site in Leber's hereditary optic neuropathy (LHON). J Biol Chem. 2004 Dec 10;279(50):51783-92. Epub 2004 Oct 6.

Both 11778/ND4 and 3460/ND1 mutations induced rotenone resistance and 11778/ND4 showed an increased K (m) for ubiquinol-2 with respect to the control group.
3(0,0,0,3) Details
9718301 Zickermann V, Barquera B, Wikstrom M, Finel M: Analysis of the pathogenic human mitochondrial mutation ND1/3460, and mutations of strictly conserved residues in its vicinity, using the bacterium Paracoccus denitrificans. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15136-41. Epub 2008 Sep 23.

The human mitochondrial ND1/3460 mutation changes Ala52 to Thr in the ND1 subunit of Complex I, and causes Leber's hereditary optic neuropathy (LHON) [Huoponen et al. (1991) Am.
The enzymatic activity of the mutants in the presence of hexammineruthenium (rotenone-insensitive) and ubiquinone-1 (rotenone-sensitive) were assayed.
3(0,0,0,3) Details
15647387 Koopman WJ, Verkaart S, Visch HJ, van der Westhuizen FH, Murphy MP, van den Heuvel LW, Smeitink JA, Willems PH: Inhibition of complex I of the electron transport chain causes O2-. -mediated mitochondrial outgrowth. J Biol Chem. 2005 Oct 14;280(41):34644-53. Epub 2005 Aug 5.

In the present study, we have used rotenone, an inhibitor of complex I of the respiratory chain, which is thought to increase mitochondrial O (2)(-)* production, and mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to investigate the relationship between mitochondrial O (2)(-)* production and morphology in human skin fibroblasts.
3(0,0,0,3) Details
10347173 Barrientos A, Moraes CT: Titrating the effects of mitochondrial complex I impairment in the cell physiology. Neurosci Lett. 1994 Aug 15;177(1-2):58-62.

We used a genetic model (40% CI-inhibited human-ape xenomitochondrial cybrids) and a drug-induced model (0-100% CI-inhibited cells using different concentrations of rotenone).
2(0,0,0,2) Details
16798828 Andrukhiv A, Costa AD, West IC, Garlid KD: Opening mitoKATP increases superoxide generation from complex I of the electron transport chain. J Biol Chem. 1999 Jun 4;274(23):16188-97.

Myxothiazol stimulated mitoK (ATP)-dependent ROS production, whereas rotenone had no effect.
2(0,0,0,2) Details
11543648 Chen JY, Tsao GC, Zhao Q, Zheng W: Differential cytotoxicity of Mn (II) and Mn (III): special reference to mitochondrial [Fe-S] containing enzymes. Brain. 2004 Oct;127(Pt 10):2183-92. Epub 2004 Sep 1.

In contrast, rotenone and MPP+ did not seem to alter mtDNA levels.
Following exposure of mitochondrial fractions with Mn (II) or Mn (III), there was a significant inhibition by either Mn species in activities of Complex I whose active site contains five to eight [Fe-S] clusters.
2(0,0,0,2) Details
11337409 Moller IM: PLANT MITOCHONDRIA AND OXIDATIVE STRESS: Electron Transport, NADPH Turnover, and Metabolism of Reactive Oxygen Species. Trans Am Ophthalmol Soc. 2007;105:379-91.

In addition to complexes I-IV, the plant mitochondrial ETC contains a non-proton-pumping alternative oxidase as well as two rotenone-insensitive, non-proton-pumping NAD (P) H dehydrogenases on each side of the inner membrane: NDex on the outer surface and NDin on the inner surface.
Complex I is the main enzyme oxidizing NADH under normal conditions and is also a major site of ROS production, together with complex III.
1(0,0,0,1) Details
14706836 Talbot DA, Lambert AJ, Brand MD: Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3. J Biol Chem. 2007 Aug 17;282(33):24146-56. Epub 2007 Jun 20.

Both superoxide production and the GDP-sensitive proton conductance were suppressed by rotenone plus an antioxidant.
1(0,0,0,1) Details
8285590 Dexter DT, Sian J, Rose S, Hindmarsh JG, Mann VM, Cooper JM, Wells FR, Daniel SE, Lees AJ, Schapira AH, et al.: Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann Neurol. 1994 Jan;35(1):38-44.

There may be some impairment of mitochondrial complex I activity in the substantia nigra in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Rotenone-sensitive NADH coenzyme Q1 reductase activity (complex I) was reduced to levels intermediate between those in control subjects and those in patients with overt Parkinson's disease, but this change did not reach statistical significance.
1(0,0,0,1) Details
8135820 Pecci L, Montefoschi G, Fontana M, Cavallini D: Aminoethylcysteine ketimine decarboxylated dimer inhibits mitochondrial respiration by impairing electron transport at complex I level. Steroids. 2006 Nov;71(11-12):984-92. Epub 2006 Sep 6.

Furthermore, the dimer did not affect the rotenone-insensitive electron transfer from NADH to menadione.
1(0,0,0,1) Details
17239993 Tsuruta T, Oh-Hashi K, Ueno Y, Kitade Y, Kiuchi K, Hirata Y: RNAi knockdown of caspase-activated DNase inhibits rotenone-induced DNA fragmentation in HeLa cells. Biochim Biophys Acta. 2001 Apr 2;1504(2-3):179-95.

Rotenone, an inhibitor of mitochondrial complex I, induces apoptosis in a variety of cells.
1(0,0,0,1) Details
16668682 Soole KL, Dry IB, Wiskich JT: Partial Purification and Characterization of Complex I, NADH:Ubiquinone Reductase, from the Inner Membrane of Beetroot Mitochondria. Eur J Neurosci. 1993 Aug 1;5(8):1029-34.

The purified NADH dehydrogenase complex catalyzed the reduction of various electron acceptors with NADH as the electron donor, was not sensitive to rotenone inhibition, and had a slow NADPH-ubiquinone 5 reductase activity.
1(0,0,0,1) Details
11100151 Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT: Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Plant Cell. 2003 May;15(5):1212-26.

We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity.
82(1,1,1,2) Details
15704879 Bufetov EN, Polygalova OO, Ponomareva AA: [Ultrastructural characteristics of mitochondria during cell adaptation to rotenone]. J Biol Chem. 2006 Mar 17;281(11):7136-42. Epub 2006 Jan 12.

A study was made of respiration, heat production, K+ output and ultrastructure of wheat root cells treated for 6 h with rotenone (10 microM), an inhibitor of HADH-ubiquinone oxidoreductase (Complex I).
81(1,1,1,1) Details
17579777 Cao Q, Wei LR, Lu LL, Zhao CL, Zhao HY, Yang H: Astrocytes protect MN9D neuronal cells against rotenone-induced oxidative stress by a glutathione-dependent mechanism. FEBS Lett. 1994 Feb 14;339(1-2):142-6.

Rotenone specifically inhibits mitochondrial complex I, and long exposure to rotenone may increase the risk for Parkinson's disease (PD) and cause Parkinsonism.
81(1,1,1,1) Details
19059197 Fato R, Bergamini C, Bortolus M, Maniero AL, Leoni S, Ohnishi T, Lenaz G: Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species. Ukr Biokhim Zh. 2003 Nov-Dec;75(6):115-22.

Our results indicate that different Complex I inhibitors can be grouped into two classes: Class A inhibitors (Rotenone, Piericidin A and Rolliniastatin 1 and 2) increase ROS production; Class B inhibitors (Stigmatellin, Mucidin, Capsaicin and Coenzyme Q (2)) prevent ROS production also in the presence of Class A inhibitors.
65(0,2,2,5) Details
14598303 Shamoto-Nagai M, Maruyama W, Kato Y, Isobe K, Tanaka M, Naoi M, Osawa T: An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH-SY5Y cells. FEBS Lett. 1996 Feb 12;380(1-2):176-8.
63(0,2,2,3) Details
17601793 Merker MP, Audi SH, Lindemer BJ, Krenz GS, Bongard RD: Role of mitochondrial electron transport complex I in coenzyme Q1 reduction by intact pulmonary arterial endothelial cells and the effect of hyperoxia. Parasitol Int. 2005 Sep;54(3):185-93.

The mitochondrial electron transport complex I inhibitor rotenone decreased the CoQ (1) reduction rate by 85% in the normoxic cells and 44% in the hyperoxia-exposed cells.
34(0,1,1,4) Details
17706244 de Wit LE, Spruijt L, Schoonderwoerd GC, de Coo IF, Smeets HJ, Scholte HR, Sluiter W: A simplified and reliable assay for complex I in human blood lymphocytes. . J Nucl Med. 1997 Jul;38(7):1155-60.

The results of the present study show that permeabilization of human blood lymphocytes in the presence of protease inhibitors by three cycles of freeze-thawing enables reproducible detection of the rotenone-sensitive complex I activity.
34(0,1,1,4) Details
10969076 Lotharius J, O'Malley KL: The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H243-50. Epub 2005 Mar 11.

Although a mean lethal dose of MPP (+) led to ROS production in identified dopaminergic neurons, toxic doses of the Complex I inhibitor rotenone did not.
33(0,1,1,3) Details
7550026 Charalambous A, Tluczek L, Frey KA, Higgins DS Jr, Greenamyre TJ, Kilbourn MR: Synthesis and biological evaluation in mice of (2-[11C] methoxy)-6',7'-dihydrorotenol, a second generation rotenoid for marking mitochondrial complex I activity. Histochem Cell Biol. 2005 Jul;124(1):69-76. Epub 2005 Jul 22.

Recently we reported the synthesis of (2-[11C] methoxy) rotenone ([11C] ROT) as a tool for in vivo studies of complex I.
33(0,1,1,3) Details
15032834 Hagedorn PH, Flyvbjerg H, Moller IM: Modelling NADH turnover in plant mitochondria. . J Cell Biochem. 2001;82(2):271-6.

It is produced by enzymes in, or associated with, the tricarboxylic acid cycle in the matrix, and it is oxidized by two respiratory chain enzymes in the inner membrane, the rotenone-sensitive complex I and the rotenone-insensitive internal NADH dehydrogenase (ND (in)).
32(0,1,1,2) Details
8627318 Davey GP, Clark JB: Threshold effects and control of oxidative phosphorylation in nonsynaptic rat brain mitochondria. Am J Physiol Cell Physiol. 2008 Feb;294(2):C460-6. Epub 2007 Dec 12.

Rotenone, myxothiazol, and KCN were used to titrate the activities of NADH:ubiquinone oxidoreductase (EC 1.6.5.3; complex I), ubiquinol:ferrocytochrome c oxidoreductase (EC 1.10.2.2; complex III), and cytochrome c oxidase (EC 1.9.3.1; complex IV ), respectively.
32(0,1,1,2) Details
18325346 MacKenzie EL, Ray PD, Tsuji Y: Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative stress. J Cell Sci. 2007 Jun 1;120(Pt 11):1908-14. Epub 2007 May 15.

Here, we describe a cytoprotective response involving transcriptional activation of the ferritin H gene in response to the mitochondrial complex I inhibitor and neurotoxic compound rotenone.
31(0,1,1,1) Details
7824183 Brouillet E, Henshaw DR, Schulz JB, Beal MF: Aminooxyacetic acid striatal lesions attenuated by 1,3-butanediol and coenzyme Q10. J Biol Chem. 2006 May 19;281(20):14250-5. Epub 2006 Mar 16.

In the present study, we show that and the specific complex I inhibitor rotenone produces a similar neurochemical profile in the striatum, consistent with an effect of AOAA on energy metabolism.
31(0,1,1,1) Details
9932647 Sreeramulu K, Schmidt CL, Schafer G, Anemuller S: Studies of the electron transport chain of the euryarcheon Halobacterium salinarum: indications for a type II NADH dehydrogenase and a complex III analog. J Bioenerg Biomembr. 1998 Oct;30(5):443-53.

Complex I inhibitors like rotenone and annonine were inactive, clearly excluding the presence of a coupled NADH dehydrogenase.
31(0,1,1,1) Details
1399827 Kawasaki S, Akiyama S, Kurokawa T, Kataoka M, Dohmitsu K, Kondoh K, Yamauchi M, Ito K, Watanabe T, Sugiyama S, et al.: Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin and mitomycin C. PLoS One. 2008 Jan 16;3(1):e1433.

As for its effective sites, SOD-POE prevented a decrease in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic reticulum and mitochondria of mouse heart muscle by ADR as observed by electron microscopy.
31(0,1,1,1) Details
17513497 Heinen A, Aldakkak M, Stowe DF, Rhodes SS, Riess ML, Varadarajan SG, Camara AK: Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels. J Appl Physiol. 2007 Aug;103(2):623-8. Epub 2007 Apr 26.

It is well known that the FADH (2)-linked substrate succinate induces reverse electron flow to complex I of the electron transport chain and that this process generates superoxide (O (2)(*-)); these effects are blocked by the complex I blocker rotenone.
31(0,1,1,1) Details
17880941 Rojo AI, Cavada C, de Sagarra MR, Cuadrado A: Chronic inhalation of rotenone or paraquat does not induce Parkinson's disease symptoms in mice or rats. J Neurochem. 1996 Jan;66(1):403-11.

A new model based on daily inoculation of neurotoxins in the nasal cavity of C57BL/6 mice for 30 days was used to evaluate risk of three complex I inhibitors, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), rotenone and paraquat.
31(0,1,1,1) Details
1333196 Ramsay RR, Singer TP: Relation of superoxide generation and lipid peroxidation to the inhibition of NADH-Q oxidoreductase by rotenone, piericidin A, and MPP+. J Neurosci Res. 2008 Nov 15;86(15):3322-30.

The addition of NADH to submitochondrial particles inhibited by agents which interrupt electron transport from NADH-Q oxidoreductase (Complex I) to Q10 (rotenone, piericidin A, and MPP+) results in superoxide formation and lipid peroxidation.
31(0,1,1,1) Details
19348888 de Wit LE, Sluiter W: Chapter 9 Reliable assay for measuring complex I activity in human blood lymphocytes and skin fibroblasts. Bioorg Med Chem. 2004 Nov 1;12(21):5525-32.

To evaluate a deficiency of complex I activity, biochemical measurements based on estimation of the mitochondrial rotenone-sensitive NADH: ubiquinone oxidoreductase activity are an important tool.
9(0,0,1,4) Details
12678433 Fernandes AS, Pereira MM, Teixeira M: Purification and characterization of the complex I from the respiratory chain of Rhodothermus marinus. Antioxid Redox Signal. 2005 May-Jun;7(5-6):662-72.

The rotenone sensitive NADH:menaquinone oxidoreductase (NDH-I or complex I) from the thermohalophilic bacterium Rhodothermus marinus has been purified and characterized.
9(0,0,1,4) Details
2493147 Ichiki T, Tanaka M, Kobayashi M, Sugiyama N, Suzuki H, Nishikimi M, Ohnishi T, Nonaka I, Wada Y, Ozawa T: Disproportionate deficiency of iron-sulfur clusters and subunits of complex I in mitochondrial encephalomyopathy. Biochemistry. 2010 Jan 26;49(3):487-92.

Rotenone-sensitive NADH-cytochrome c reductase activity was found to be decreased in all the tissues examined.
5(0,0,0,5) Details
18414996 Benit P, Slama A, Rustin P: Decylubiquinol impedes mitochondrial respiratory chain complex I activity. Free Radic Biol Med. 2003 Feb 15;34(4):478-88.

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19252983 Racay P, Tatarkova Z, Chomova M, Hatok J, Kaplan P, Dobrota D: Mitochondrial calcium transport and mitochondrial dysfunction after global brain ischemia in rat hippocampus. PLoS One. 2010 Jan 19;5(1):e8762.


Ischemia induced progressive inhibition of complex I, affecting final electron transfer to decylubiquinone.
5(0,0,0,5) Details
9163527 Ghelli A, Benelli B, Esposti MD: Measurement of the membrane potential generated by complex I in submitochondrial particles. J Biol Chem. 2008 Oct 24;283(43):29292-300. Epub 2008 Aug 7.

5(0,0,0,5) Details
12069106 Chan TS, Teng S, Wilson JX, Galati G, Khan S, O'Brien PJ: Coenzyme Q cytoprotective mechanisms for mitochondrial complex I cytopathies involves NAD (P) H: quinone oxidoreductase 1 (NQO1). Pigment Cell Res. 2003 Oct;16(5):553-9.

In the following, using hepatocytes as a model cell, we have shown for the first time that the cytotoxicity caused by complex I inhibition by rotenone but not that caused by complex III inhibition by antimycin can be prevented by coenzyme Q (CoQ1) or menadione.
5(0,0,0,5) Details
11960602 Detaille D, Guigas B, Leverve X, Wiernsperger N, Devos P: Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Toxicol Sci. 2004 May;79(1):137-46. Epub 2004 Feb 19.

From recent findings about the indirect effect of metformin (MET) targeted on the respiratory chain complex I, we reconsidered this question and tried to determine the causality of any alteration at this enzymatic level using Xenopus laevis oocytes.
Addition of MET (50 microM) reduced by 40% the rotenone-sensitive activity of complex I only in incubating intact oocytes but not in mitochondria isolated by differential centrifugation.
3(0,0,0,3) Details
16818739 Yi JS, Holbrook BC, Michalek RD, Laniewski NG, Grayson JM: Electron transport complex I is required for CD8+ T cell function. . FEBS Lett. 1997 Jun 30;410(2-3):467-9.

To block mitochondrial function, transgenic CD8+ T cells were incubated with increasing doses of rotenone, an inhibitor of electron transport complex I.
3(0,0,0,3) Details
16410242 Schonfeld P, Reiser G: Rotenone-like action of the branched-chain phytanic acid induces oxidative stress in mitochondria. Neurochem Res. 2009 Apr;34(4):746-54. Epub 2008 Sep 19.

With succinate alone, Phyt suppresses O (2)(.) generation caused by reverse electron transport from succinate to complex I.
2(0,0,0,2) Details
18615737 Sala G, Trombin F, Beretta S, Tremolizzo L, Presutto P, Montopoli M, Fantin M, Martinuzzi A, Carelli V, Ferrarese C: Antioxidants partially restore glutamate transport defect in leber hereditary optic neuropathy cybrids. J Neurosci Res. 2008 Nov 15;86(15):3331-7.

Despite the important role of respiratory chain deficiency and oxidative stress induced by mtDNA point mutations affecting complex I, excitotoxic injury has been postulated as a concurrent pathogenic factor.
Rotenone, a classic complex I inhibitor, did not worsen the glutamate uptake defect present in LHON cybrids under basal conditions but significantly reduced glutamate transport in control cybrids.
2(0,0,0,2) Details
20307667 Greene JG, Dingledine R, Greenamyre JT: Neuron-selective changes in RNA transcripts related to energy metabolism in toxic models of parkinsonism in rodents. Biochem J. 2004 Sep 1;382(Pt 2):511-7.

Mitochondrial complex I inhibition by rotenone or MPTP can induce SNDA neurodegeneration and recapitulate motor disability in rodents.
We performed a transcriptional analysis of the midbrain response to complex I inhibition focused on selected metabolic transcripts using quantitative real-time RT-PCR in conjunction with laser-capture microdissection (LCM) of immunofluorescently-targeted SNDA and ventral tegmental area (VTA) DA neurons.
2(0,0,0,2) Details
8804391 da Silva MV, Alves PC, Duarte M, Mota N, Lobo-da-Cunha A, Harkness TA, Nargang FE, Videira A: Disruption of the nuclear gene encoding the 20.8-kDa subunit of NADH: ubiquinone reductase of Neurospora mitochondria. Science. 2007 Jun 1;316(5829):1345-8.

The nuclear gene coding for the 20.8-kDa subunit of the membrane arm of respiratory chain NADH: ubiquinone reductase (Complex I) from Neurospora crassa, nuo-20.8, was localized on linkage group I of the fungal genome.
The NADH: ubiquinone reductase activity of sonicated mitochondria from the mutant is rotenone insensitive.
2(0,0,0,2) Details
10717001 Weinberg JM, Venkatachalam MA, Roeser NF, Nissim I: Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates. Biochem Int. 1987 Apr;14(4):735-9.

Rotenone, but not antimycin or oligomycin, prevented this effect, indicating that electron transport in complex I, rather than F (1) F (0)-ATPase activity, had been responsible for maintenance of DeltaPsi (m) by the substrates.
Thus, tubule cells subjected to hypoxia/reoxygenation can have persistent energy deficits associated with complex I dysfunction for substantial periods of time before onset of the mitochondrial permeability transition and/or loss of cytochrome c.
2(0,0,0,2) Details
9475856 Yajid F, Mercier JG, Mercier BM, Dubouchaud H, Prefaut C: Effects of 4 wk of hindlimb suspension on skeletal muscle mitochondrial respiration in rats. Free Radic Biol Med. 2000 Jan 15;28(2):235-50.

With succinate + rotenone, there was no significant difference in the respiratory rate compared with the respective control group, whatever the mitochondrial origin (SS, or IMF, or from single muscle).
We conclude that 4 wk of hindlimb suspension alters the respiration of IMF mitochondria in hindlimb skeletal muscles and seems to act negatively on complex I of the electron-transport chain or prior sites.
1(0,0,0,1) Details
17428841 Koopman WJ, Verkaart S, Visch HJ, van Emst-de Vries S, Nijtmans LG, Smeitink JA, Willems PH: Human NADH:ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology?. Neuroscience. 2007 Jul 13;147(3):592-8. Epub 2007 Jun 20.


Malfunction of NADH:ubiquinone oxidoreductase or complex I (CI), the first and largest complex of the mitochondrial oxidative phosphorylation system, has been implicated in a wide variety of human disorders.
1(0,0,0,1) Details
15337616 Kaplanova V, Zeman J, Hansikova H, Cerna L, Houst'kova H, Misovicova N, Houstek J: Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family. J Biol Chem. 2001 Oct 19;276(42):38808-13. Epub 2001 Jul 30.


Although enzyme assay showed reduction of complex I activity, our results give additional support to the hypothesis that expression of LHON mutation depends on complex nuclear-mitochondrial interaction.
1(0,0,0,1) Details
7941733 Buschges R, Bahrenberg G, Zimmermann M, Wolf K: NADH: ubiquinone oxidoreductase in obligate aerobic yeasts. J Neurochem. 1994 Nov;63(5):1987-90.

The strictly aerobic yeasts Candida pinus, Cryptococcus albidus, Rhodotorula minuta, Rhodotorula mucilaginosa and Trichosporon beigelii possess mitochondrial NADH dehydrogenases with significant features of the NADH:ubiquinone oxidoreductase (complex I).
These species show in all growth phases and under standard cultivation conditions, NADH dehydrogenases of approximately 700 kDa, which are sensitive to rotenone, a specific inhibitor of this complex.
1(0,0,0,1) Details
20095467 Cheng Y, Ren M, Niu Y, Qiao J, Aneba S, Chorvat D Jr, Chorvatova A: [Assessment of mitochondrial metabolic oxidative state in living cardiomyocytes with spectrally-resolved fluorescence lifetime spectroscopy of NAD (P) H]. Plant Physiol. 1992 Feb;98(2):588-594.

Rotenone, the inhibitor of Complex I of the mitochondrial respiratory chain, increased AF intensity and shortened the average fluorescence lifetime.
Rotenone, the inhibitor of Complex I of the mitochondrial respiratory chain, increased AF intensity and shortened the average fluorescence lifetime.
1(0,0,0,1) Details
9256232 Igamberdiev AU, Bykova NV, Gardestrom P: Involvement of cyanide-resistant and rotenone-insensitive pathways of mitochondrial electron transport during oxidation of glycine in higher plants. Neurosci Lett. 2009 Jul 31;459(1):11-5. Epub 2009 May 4.

The involvement of different paths of electron transport in mitochondria during operation of glycine decarboxylase complex (GDC) was tested in different conditions, using aminoacetonitrile (AAN), the inhibitor of glycine oxidation in mitochondria, rotenone, the inhibitor of Complex I of mitochondrial electron transport, and inhibitors of cytochrome oxidase and alternative oxidase.
1(0,0,0,1) Details
9449429 Nakao N, Nakai K, Itakura T: Metabolic inhibition enhances selective toxicity of L-DOPA toward mesencephalic dopamine neurons in vitro. J Appl Physiol. 2008 Dec;105(6):1706-13. Epub 2008 Sep 18.

We investigated whether metabolic inhibition with rotenone, an inhibitor of complex I of the mitochondrial respiratory chain, may enhance the toxicity of L-DOPA toward DA neurons in mesencephalic cultures.
We investigated whether metabolic inhibition with rotenone, an inhibitor of complex I of the mitochondrial respiratory chain, may enhance the toxicity of L-DOPA toward DA neurons in mesencephalic cultures.
1(0,0,0,1) Details
16085644 Shang T, Joseph J, Hillard CJ, Kalyanaraman B: Death-associated protein kinase as a sensor of mitochondrial membrane potential: role of lysosome in mitochondrial toxin-induced cell death. Free Radic Biol Med. 2001 Nov 15;31(10):1216-27.

We have investigated here the mechanism of dephosphorylation and activation of death-associated protein kinase (DAPK) and the role of lysosome in neuroblastoma cells (SH-SY5Y) treated with mitochondrial toxins, such as MPP (+) and rotenone.
Complex I inhibition by mitochondrial toxins (e.g.
1(0,0,0,1) Details
15111504 Ye G, Metreveli NS, Donthi RV, Xia S, Xu M, Carlson EC, Epstein PN: Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes. Biochim Biophys Acta. 2002 Feb 15;1553(3):249-60.

Chronic overexpression of catalase or acute in vitro treatment with rotenone, an inhibitor of mitochondrial complex I, or thenoyltrifluoroacetone, an inhibitor of mitochondrial complex II, eliminated excess ROS production in diabetic cardiomyocytes.
Chronic overexpression of catalase or acute in vitro treatment with rotenone, an inhibitor of mitochondrial complex I, or thenoyltrifluoroacetone, an inhibitor of mitochondrial complex II, eliminated excess ROS production in diabetic cardiomyocytes.
1(0,0,0,1) Details
8875956 Corsini E, Schubert C, Marinovich M, Galli CL: Role of mitochondria in tributyltin-induced interleukin-1alpha production in murine keratinocytes. Neuroscience. 2005;135(4):1087-94. Epub 2005 Sep 8.

TBT induced a direct and concentration-related activation of NF-(kappa) B, which peaked at 2 h and was blocked by pyrrolidinedithiocarbamate, a potent NF-(kappa) B inhibitor, and rotenone, an inhibitor of the electron entry from complex I to ubiquinone.
TBT induced a direct and concentration-related activation of NF-(kappa) B, which peaked at 2 h and was blocked by pyrrolidinedithiocarbamate, a potent NF-(kappa) B inhibitor, and rotenone, an inhibitor of the electron entry from complex I to ubiquinone.
1(0,0,0,1) Details
4039407 Mendis AH, Townson S: Evidence for the occurrence of respiratory electron transport in adult Brugia pahangi and Dipetalonema viteae. Eur J Biochem. 2003 Dec;270(24):4942-51.

When assayed as separate unisexual groups, the oxygen uptake of male and female macrofilariae of both species was inhibited by classical inhibitors of respiratory electron transport (RET), and showed classical substrate bypass phenomena in response to succinate and ascorbate, N,N,N',N'-tetramethyl-p-phenylenediamine with respect to the RET inhibitors rotenone (inhibitor of complex I) and antimycin A (inhibitor of complex III).
When assayed as separate unisexual groups, the oxygen uptake of male and female macrofilariae of both species was inhibited by classical inhibitors of respiratory electron transport (RET), and showed classical substrate bypass phenomena in response to succinate and ascorbate, N,N,N',N'-tetramethyl-p-phenylenediamine with respect to the RET inhibitors rotenone (inhibitor of complex I) and antimycin A (inhibitor of complex III).
1(0,0,0,1) Details
19067348 Mortiboys H, Thomas KJ, Koopman WJ, Klaffke S, Abou-Sleiman P, Olpin S, Wood NW, Willems PH, Smeitink JA, Cookson MR, Bandmann O: Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Mol Biochem Parasitol. 1985 Mar;14(3):337-54.

RESULTS: Parkin-mutant cells had lower mitochondrial complex I activity and complex I-linked adenosine triphosphate production, which correlated with a greater degree of mitochondrial branching, suggesting that the functional and morphological effects of parkin are related.
Fluorescence recovery after photobleaching assays demonstrated a lower level of functional connectivity of the mitochondrial matrix, which further worsened after rotenone exposure.
1(0,0,0,1) Details
19232380 Kawasaki A, Hayashi T, Nakachi K, Trosko JE, Sugihara K, Kotake Y, Ohta S: Modulation of connexin 43 in rotenone-induced model of Parkinson's disease. Neuroscience. 2009 Apr 21;160(1):61-8. Epub 2009 Feb 13.

In this study, we show that a major gap junctional protein, connexin43 (Cx43), in astrocytes is enhanced both in a rat Parkinson's disease (PD) model induced with rotenone, a widely used pesticide that inhibits mitochondrial complex I, and in vitro in cultured astrocytes stimulated with rotenone.
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16666054 Day DA, Moore AL, Dry IB, Wiskich JT, Azcon-Bieto J: Regulation of Nonphosphorylating Electron Transport Pathways in Soybean Cotyledon Mitochondria and Its Implications for Fat Metabolism. EMBO J. 1998 Aug 17;17(16):4848-58.

Despite substantial rotenone-resistant O (2) uptake with NAD-linked substrates, respiratory control was observed in the presence of antimycin, indicating restriction of electron flow through complex I.
81(1,1,1,1) Details
17298981 Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, Rossignol R: Mitochondrial bioenergetics and structural network organization. Eur J Biochem. 1987 Dec 15;169(3):585-91.

Second, we followed the effect of rotenone, a specific inhibitor of respiratory chain complex I, which causes large structural perturbations, once a threshold was reached.
81(1,1,1,1) Details
19495970 Villa RF, Gorini A, Hoyer S: Effect of Ageing and Ischemia on Enzymatic Activities Linked to Krebs' Cycle, Electron Transfer Chain, Glutamate and Aminoacids Metabolism of Free and Intrasynaptic Mitochondria of Cerebral Cortex. Neurosci Lett. 2002 Nov 15;333(1):25-8.

The maximum rate (V (max)) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate- and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction.
81(1,1,1,1) Details
6713449 Quinn PJ, Crutcher EC: The action of beta-adrenoceptor antagonists on rat heart mitochondrial function in vitro: a comparison of propranolol, timolol, and atenolol. Cardiovasc Res. 1984 Apr;18(4):212-9.

Transfer of electrons through Complex I measured by the rate of reduction of ferricyanide by submitochondrial particles inhibited by rotenone and the lack of specific inhibition by propranolol of succinate supported respiration indicated that one site of drug action was between NADH dehydrogenase and its associated flavoprotein, possibly close to the site of rotenone inhibition.
81(1,1,1,1) Details
1932041 Bironaite DA, Cenas NK, Kulys JJ: The rotenone-insensitive reduction of quinones and nitrocompounds by mitochondrial NADH:ubiquinone reductase. Biochemistry. 2008 Oct 7;47(40):10816-26. Epub 2008 Sep 10.

The rotenone-insensitive reduction of quinones and aromatic nitrocompounds by mitochondrial NADH: ubiquinone reductase (complex I, EC 1.6.99.3) has been studied.
81(1,1,1,1) Details
12097231 Li C, Wright MM, Jackson RM: Reactive species mediated injury of human lung epithelial cells after hypoxia-reoxygenation. Neurobiol Dis. 2010 Mar 19.

Rotenone and myxothiazole increased DCF oxidation more in hypoxic than in normoxic cells, suggesting that mitochondrial electron transport complex I may have been altered by hypoxia preexposure.
81(1,1,1,1) Details
11074592 Gniadecki R, Thorn T, Vicanova J, Petersen A, Wulf HC: Role of mitochondria in ultraviolet-induced oxidative stress. Biochem Biophys Res Commun. 1992 Jul 31;186(2):698-705.

The same effect was seen after incubation with rotenone, which blocks electron flow from NADH-reductase (complex I) to ubiquinone.
81(1,1,1,1) Details
11527970 Chauvin C, De Oliveira F, Ronot X, Mousseau M, Leverve X, Fontaine E: Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells. Biochimie. 2002 Dec;84(12):1189-97.

Because functional links between the PTP and the respiratory chain complex I have been reported, we have investigated the effects of rotenone on PTP regulation in U937 and KB cells.
63(0,2,2,3) Details
16174799 Chen Q, Hoppel CL, Lesnefsky EJ: Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria. J Pharmacol Exp Ther. 2006 Jan;316(1):200-7. Epub 2005 Sep 20.

Irreversible blockade of electron transport at complex I by rotenone decreases ischemic damage to cardiac mitochondria by decreasing the loss of cytochrome c and preserving respiration through cytochrome oxidase.
62(0,2,2,2) Details
11707688 Yuhki KI, Miyauchi T, Kakinuma Y, Murakoshi N, Maeda S, Goto K, Yamaguchi I, Suzuki T: Endothelin-1 production is enhanced by rotenone, a mitochondrial complex I inhibitor, in cultured rat cardiomyocytes. Brain Res. 2008 Jun 18;1215:208-17. Epub 2008 Apr 12.
62(0,2,2,2) Details
9878712 Ushakova AV, Grivennikova VG, Ohnishi T, Vinogradov AD: Triton X-100 as a specific inhibitor of the mammalian NADH-ubiquinone oxidoreductase (Complex I). FEMS Yeast Res. 2006 Dec;6(8):1117-29.

Also similar to rotenone, Triton X-100 partially protects Complex I against the thermally induced deactivation and partially activates the thermally deactivated enzyme.
34(0,1,1,4) Details
10908294 Nakamura K, Bindokas VP, Marks JD, Wright DA, Frim DM, Miller RJ, Kang UJ: The selective toxicity of 1-methyl-4-phenylpyridinium to dopaminergic neurons: the role of mitochondrial complex I and reactive oxygen species revisited. J Biol Chem. 2004 Jul 23;279(30):31121-30. Epub 2004 May 19.

In contrast, the specific complex I inhibitor rotenone, at a dose (20 nM) that was less toxic than MPP (+) to dopaminergic neurons, depolarized DeltaPsim to a greater extent than MPP (+).
34(0,1,1,4) Details
18385062 He Y, Leung KW, Zhang YH, Duan S, Zhong XF, Jiang RZ, Peng Z, Tombran-Tink J, Ge J: Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: protection by antioxidants. Eur J Pharmacol. 2001 Nov 16;431(2):163-70.

Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyltrifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC).
33(0,1,1,3) Details
14663204 Sakka N, Sawada H, Izumi Y, Kume T, Katsuki H, Kaneko S, Shimohama S, Akaike A: Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone. Int J Biochem Cell Biol. 2009 Aug-Sep;41(8-9):1697-707. Epub 2009 Mar 3.

We investigated the involvement of superoxide and endogenous dopamine in neurotoxicity by rotenone, a complex I inhibitor.
32(0,1,1,2) Details
10515594 Bailey SM, Pietsch EC, Cunningham CC: Ethanol stimulates the production of reactive oxygen species at mitochondrial complexes I and III. Exp Cell Res. 2001 Oct 15;270(1):56-65.

Rotenone, a mitochondrial complex I inhibitor that allows electron flow through the flavin mononucleotide (FMN), but prevents electron flow to complex III, significantly increased reactive oxygen species production in untreated cells, but decreased reactive oxygen species production in antimycin plus ethanol-treated cells.
32(0,1,1,2) Details
8566093 Santiago M, Granero L, Machado A, Cano J: Complex I inhibitor effect on the nigral and striatal release of dopamine in the presence and absence of nomifensine. Diabetes. 2004 Apr;53(4):1052-9.

The effect of inhibitors of complex I respiratory chain--1-methyl-4-phenylpyridinium ion (MPP+, 10 microM) and rotenone (100 microM)--on the release and metabolism of dopamine was studied by in vivo microdialysis in the striatum and substantia nigra.
32(0,1,1,2) Details
16449798 Hsieh CC, Papaconstantinou J: Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived Snell dwarf mice. Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2067-74. Epub 2006 Jun 23.

Here we propose that activation of the p38 MAPK pathway by complex I (CI) generated ROS, in response to rotenone (ROT) treatment, is based on the ability of reduced Trx to bind to and inhibit ASK 1 and its release from the complex upon oxidation.
31(0,1,1,1) Details
12515859 Miyadera H, Shiomi K, Ui H, Yamaguchi Y, Masuma R, Tomoda H, Miyoshi H, Osanai A, Kita K, Omura S: Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase). Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):473-7. Epub 2003 Jan 6.

The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes.
31(0,1,1,1) Details
10398297 Duan W, Mattson MP: Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease. Diabetes. 2004 May;53(5):1336-43.

The 2-DG treatment suppressed oxidative stress, preserved mitochondrial function, and attenuated cell death in cultured dopaminergic cells exposed to the complex I inhibitor rotenone or Fe2+. 2-DG and DR induced expression of the stress proteins heat-shock protein 70 and glucose-regulated protein 78 in dopaminergic cells, suggesting involvement of these cytoprotective proteins in the neuroprotective actions of 2-DG and DR.
31(0,1,1,1) Details
14766935 Cheranov SY, Jaggar JH: Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries. J Invest Dermatol. 1996 Nov;107(5):720-5.

CCCP (a protonophore; 1 microm) and rotenone (an electron transport chain complex I inhibitor; 10 microm) depolarized mitochondria, reduced Ca (2+) spark and wave frequency, and elevated global [Ca (2+)](i) in smooth muscle cells of intact arteries.
31(0,1,1,1) Details
2170057 Yamamoto M, Akiyama C, Aikawa H: D-penicillamine-induced copper deficiency in suckling mice: neurological abnormalities and brain mitochondrial enzyme activities. J Pharmacol Sci. 2003 Jun;92(2):137-42.

Cytochrome c oxidase activity (complex IV) in the brain showed 51% decrease of the controls, on the contrary, rotenone-sensitive NADH cytochrome c reductase (complex I + III) and succinate cytochrome c reductase (complex II + III) were normal.
31(0,1,1,1) Details
19635391 Monroe RK, Halvorsen SW: Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption. Int J Biochem. 1994 Sep;26(9):1119-27.

Exposure of BE (2)-C cells to the heavy metals CdCl (2) and HgCl (2) and to the mitochondrial complex I inhibitor rotenone inhibited interleukin-6, interferon-gamma and ciliary neurotrophic factor-mediated Jak/STAT signaling, reduced Jak1 and Jak2 auto-phosphorylation and induced Jak tyrosine nitration.
31(0,1,1,1) Details
14681995 Tkachenko HM, Kurhaliuk NM, Vovkanych LS: [Role of ATP-sensitive potassium channel activators in liver mitochondrial function in rats with different resistance to hypoxia]. Biochem J. 2008 Jan 15;409(2):491-9.

Additional analyses contain the next inhibitors: mitochondrial fermentative complex I-10 mkM rotenone, succinate dehydrogenase 2 mM malonic acid.
31(0,1,1,1) Details
19520091 Long J, Ma J, Luo C, Mo X, Sun L, Zang W, Liu J: Comparison of two methods for assaying complex I activity in mitochondria isolated from rat liver, brain and heart. J Neurochem. 2005 Jun;93(5):1199-208.

SIGNIFICANCE: Considering the important contribution of the non-specific rotenone-insensitive activity in the complex I assay, it is suggested that the NADH method with BSA addition should be adopted for assaying complex I activity in the brain or liver samples, while the DCIP method is the better choice for heart samples.
8(0,0,1,3) Details
17463293 Tanaka-Esposito C, Chen Q, Moghaddas S, Lesnefsky EJ: Ischemic preconditioning does not protect via blockade of electron transport. J Pharmacol Exp Ther. 2006 Dec;319(3):1405-12. Epub 2006 Sep 21.

Maximally expressed complex I activity measured as rotenone-sensitive NADH:ubiquinone oxidoreductase in detergent-solubilized mitochondria was also unaffected by IPC.
8(0,0,1,3) Details
15248896 DeHaan C, Habibi-Nazhad B, Yan E, Salloum N, Parliament M, Allalunis-Turner J: Mutation in mitochondrial complex I ND6 subunit is associated with defective response to hypoxia in human glioma cells. Free Radic Biol Med. 1999 Oct;27(7-8):891-900.

The T14634C mutation did not abrogate ND6 protein expression, however, M010b cells were more resistant to rotenone, an agent used to screen for Complex I mutations, and adriamycin, an agent activated by redox cycling.
5(0,0,0,5) Details
8294484 Herz U, Schroder W, Liddell A, Leaver CJ, Brennicke A, Grohmann L: Purification of the NADH:ubiquinone oxidoreductase (complex I) of the respiratory chain from the inner mitochondrial membrane of Solanum tuberosum. J Neurochem. 1993 Oct;61(4):1546-8.

The enzyme preparation showed an NADH:ubiquinone-2 reductase activity of 11.5 mumol x min-1 x mg-1 and is strongly inhibited by rotenone.
5(0,0,0,5) Details
10462447 Tormo JR, Gonzalez MC, Cortes D, Estornell E: Kinetic characterization of mitochondrial complex I inhibitors using annonaceous acetogenins. Neurochem Int. 2007 Jan;50(1):139-47. Epub 2006 Sep 11.

4(0,0,0,4) Details
17339833 Hinke SA, Martens GA, Cai Y, Finsi J, Heimberg H, Pipeleers D, Van de Casteele M: Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer. Mol Cell Biol. 1995 Feb;15(2):964-74.

BACKGROUND AND PURPOSE: Two mechanisms have been proposed to explain the insulin-sensitising properties of metformin in peripheral tissues: (a) inhibition of electron transport chain complex I, and (b) activation of the AMP activated protein kinase (AMPK).
In rat beta-cells, metformin caused NAD (P) H accumulation above maximal glucose-inducible levels, mimicking the effect of rotenone.
4(0,0,0,4) Details
15262965 Lambert AJ, Brand MD: Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I). J Physiol. 2001 Oct 1;536(Pt 1):211-24.

Despite complete inhibition of NADH: ubiquinone oxidoreductase activity in each case, different classes of quinone-binding site inhibitor (rotenone, piericidin, and high concentrations of myxothiazol) gave different rates of superoxide production during forward electron transport (the rate with myxothiazol was twice that with rotenone) suggesting that the site of rapid superoxide generation by complex I is in the region of the ubisemiquinone-binding sites and not upstream at the flavin or low potential FeS centers.
4(0,0,0,4) Details
7777208 Blandini F, Porter RH, Greenamyre JT: Autoradiographic study of mitochondrial complex I and glutamate receptors in the basal ganglia of rats after unilateral subthalamic lesion. FEBS J. 2005 Apr;272(7):1649-59.

3(0,0,0,3) Details
14963044 Batandier C, Leverve X, Fontaine E: Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I. J Neurol Neurosurg Psychiatry. 1993 May;56(5):477-80.

Moreover, PTP opening decreased rotenone-sensitive NADH ubiquinone reductase activity, whereas it did not affect the NADH FeCN reductase activity.
3(0,0,0,3) Details
19821036 Shiryaeva A, Arkadyeva A, Emelyanova L, Sakuta G, Morozov V: Superoxide anion production by the mitochondrial respiratory chain of hepatocytes of rats with experimental toxic hepatitis. FEMS Microbiol Lett. 2004 Aug 1;237(1):139-45.

The purpose of this study was to examine our previously formulated assumption concerning the predominant contribution of the complex I to O (2)(*-) production increase by the mitochondrial respiratory chain of hepatocytes in toxic hepatitis (Shiryaeva et al.
The rates of O (2)(*-) production by SP of rats with toxic hepatitis in the presence of NADH or NADH+ rotenone were similar.
2(0,0,0,2) Details
1463844 Ellersiek U, Steinmuller K: Cloning and transcription analysis of the ndh (A-I-G-E) gene cluster and the ndhD gene of the cyanobacterium Synechocystis sp. J Biol Chem. 2002 Sep 6;277(36):33249-57. Epub 2002 Jun 21.

The plastid DNA of higher plants contains eleven reading frames that are homologous to subunits of the mitochondrial NADH-ubiquinone oxidoreductase (complex I).
The enzyme is sensitive to rotenone and is located on the cytoplasmic and the thylakoid membrane.
2(0,0,0,2) Details
16357365 Brueckl C, Kaestle S, Kerem A, Habazettl H, Krombach F, Kuppe H, Kuebler WM: Hyperoxia-induced reactive oxygen species formation in pulmonary capillary endothelial cells in situ. Arthritis Rheum. 2003 Mar;48(3):700-8.

ROS and [Ca (2+)](i) responses were blocked by the mitochondrial complex I inhibitor rotenone, whereas inhibitors of NAD (P) H oxidase and the intracellular Ca (2+) chelator BAPTA predominantly attenuated the late phase of the hyperoxia-induced DCF fluorescence increase after > 30 min.
ROS and [Ca (2+)](i) responses were blocked by the mitochondrial complex I inhibitor rotenone, whereas inhibitors of NAD (P) H oxidase and the intracellular Ca (2+) chelator BAPTA predominantly attenuated the late phase of the hyperoxia-induced DCF fluorescence increase after > 30 min.
1(0,0,0,1) Details
2539917 Rossi SC, Wetterhahn KE: Chromium (V) is produced upon reduction of chromate by mitochondrial electron transport chain complexes. J Biol Chem. 1993 Oct 25;268(30):22914-9.

Rotenone, antimycin and cyanide all produced approximately 40% inhibition of the NADH-dependent chromate-reductase activity.
Thus, complex I (NADH:ubiquinone oxidoreductase) appears to be responsible for the inhibitor-insensitive, and complex IV (ferrocytochrome c:oxygen oxidoreductase) for the inhibitor-sensitive NADH-dependent chromium (VI) reduction and chromium (V) formation.
1(0,0,0,1) Details
12013844 Miki T: [Inhibitors of complex I and II of the mitochondrial respiratory chain] Am J Respir Cell Mol Biol. 2006 Apr;34(4):453-63. Epub 2005 Dec 15.

1(0,0,0,1) Details
17438209 Tong JJ: Mitochondrial delivery is essential for synaptic potentiation. Somat Cell Mol Genet. 1985 Jul;11(4):345-52.

Rotenone, an inhibitor of mitochondrial electron transport chain complex I, suppresses mitochondrial transport and abolishes the potentiation of the synapse.
Rotenone, an inhibitor of mitochondrial electron transport chain complex I, suppresses mitochondrial transport and abolishes the potentiation of the synapse.
1(0,0,0,1) Details
11693180 Yasutake A, Hirayama K: Evaluation of methylmercury biotransformation using rat liver slices. Arch Toxicol. 2001 Sep;75(7):400-6.

Rotenone, an inhibitor of complex I in the mitochondrial electron transport system, increased levels of both inorganic Hg and lipid peroxide.
Rotenone, an inhibitor of complex I in the mitochondrial electron transport system, increased levels of both inorganic Hg and lipid peroxide.
1(0,0,0,1) Details
10370869 Zini R, Morin C, Bertelli A, Bertelli AA, Tillement JP: Effects of resveratrol on the rat brain respiratory chain. Mol Microbiol. 1999 Aug;33(3):590-8.

This property is especially interesting as this complex is the site where reactive oxygen substances (ROS) are generated.
The rate of oxygen consumption by the different complexes was checked using rotenone (2 microM), malonate (10 mM), antimycin A (1 microM), potassium cyanide (KCN) (0.3 mM) and oligomycin (10 microM) to inhibit complexes II, III, IV, V and I, respectively.
1(0,0,0,1) Details
18551278 Lin PC, Puhar A, Steuber J: NADH oxidation drives respiratory Na+ transport in mitochondria from Yarrowia lipolytica. J Bioenerg Biomembr. 1993 Aug;25(4):377-84.

NADH-driven Na+ transport was sensitive towards rotenone, a specific inhibitor of complex I.
82(1,1,1,2) Details
15722109 Capel F, Rimbert V, Lioger D, Diot A, Rousset P, Mirand PP, Boirie Y, Morio B, Mosoni L: Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved. Neuroreport. 2003 Dec 19;14(18):2425-8.

Rotenone abolished this increase, demonstrating that it was due to a free radical release during reverse electron transfer from complex II towards complex I.
81(1,1,1,1) Details
18438923 Parihar MS, Kunz EA, Brewer GJ: Age-related decreases in NAD (P) H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons. Biochem Soc Trans. 1999 Aug;27(4):586-91.

With complex I of the electron transport chain inhibited by rotenone, treatment with glutamate or ionomycin only resulted in the increase in NAD (P) H fluorescence.
81(1,1,1,1) Details
20098733 Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG, Reichmann H, Funk RH: Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice. J Neurosci. 1995 Sep;15(9):5912-8.

Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients.
81(1,1,1,1) Details
19777565 Deng YT, Huang HC, Lin JK: Rotenone induces apoptosis in MCF-7 human breast cancer cell-mediated ROS through JNK and p38 signaling. J Biol Chem. 1986 Mar 5;261(7):3060-7.

Rotenone is an inhibitor of the mitochondrial electron transport chain complex I, resulting in the generation of reactive oxygen species (ROS).
81(1,1,1,1) Details
15143528 Tkachenko HM, Moibenko OO, Kurhaliuk NM: [Effect of ATP-sensitive potassium channel modulators and intermittent hypoxia on mitochondrial respiration during stress]. J Bioenerg Biomembr. 2003 Oct;35(5):439-50.

We used next substrates of oxidation--0.35 mM succinate, 1 mM alpha-ketoglutarate, 3 mM glutamate, 3 mM pyruvate, 2.5 mM malate and inhibitor of the mitochondrial fermentative complex I (10 microM rotenone), succinate dehydrogenase inhibitor (2 mM malonate) and inhibitor of transamination (1 mM aminooxiacetate).
81(1,1,1,1) Details
16004991 Wang G, Qi C, Fan GH, Zhou HY, Chen SD: PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone. J Cardiovasc Pharmacol. 2001 Dec;38(6):850-8.
62(0,2,2,2) Details
11358527 Fang J, Wang Y, Beattie DS: Isolation and characterization of complex I, rotenone-sensitive NADH: ubiquinone oxidoreductase, from the procyclic forms of Trypanosoma brucei. Am J Clin Nutr. 2002 Nov;76(5):1031-9.

Both proline:cytochrome c reductase and NADH:ubiquinone oxidoreductase of procyclic T. brucei were inhibited by the specific inhibitors of complex I rotenone, piericidin A, and capsaicin.
44(0,1,3,4) Details
12428729 Stephans SE, Miller GW, Levey AI, Greenamyre JT: Acute mitochondrial and chronic toxicological effects of 1-methyl-4-phenylpyridinium in human neuroblastoma cells. Annu Rev Plant Physiol Plant Mol Biol. 2001 Jun;52:561-591.

The lipophilic complex I inhibitor, rotenone, increased proton excretion in both cell lines.
38(0,1,2,3) Details
3927493 Garnett KE, Simmons WA, Wing MS, Breen GA: DNA-mediated transfer of complex I genes into three different respiration-deficient Chinese hamster mutant cell lines with defects in complex I of electron transport chain. Yeast. 1994 Apr;10(4):475-9.

Evidence for the DNA-mediated transformation of these respiration-deficient cells with a putative complex I gene includes: the clones are respiration-positive and respire at rates comparable to those of wild-type human, hamster, or mouse cells; the clones have rotenone-sensitive NADH oxidase activities, indicating a functional complex I of the electron transport chain; and the clones appear to be true transformants, as demonstrated by hybridization and Southern blot analyses.
34(0,1,1,4) Details
3930501 Gondal JA, Anderson WM: The molecular morphology of bovine heart mitochondrial NADH----ubiquinone reductase. J Biol Chem. 1985 Oct 15;260(23):12690-4.

Cross-linking of complex I with DSP for 2 min in the presence of 1 microM rotenone yielded a cross-linked product consisting of the two natural disulfide-linked subunits and the 110-115- and 69-kDa polypeptides.
34(0,1,1,4) Details
11714483 Zhang JG, Nicholls-Grzemski FA, Tirmenstein MA, Fariss MW: Vitamin E succinate protects hepatocytes against the toxic effect of reactive oxygen species generated at mitochondrial complexes I and III by alkylating agents. J Mol Cell Cardiol. 2005 Jul;39(1):149-58.

In addition, the treatment with either rotenone (ROT, a complex I inhibitor) or antimycin A (AA, a complex III inhibitor) potentiated EMS-induced lipid peroxidation and necrotic cell death which were again completely prevented by TS treatment.
32(0,1,1,2) Details
11281291 Schuchmann S, Heinemann U: Increased mitochondrial superoxide generation in neurons from trisomy 16 mice: a model of Down's syndrome. Neurotoxicology. 2002 Oct;23(4-5):569-80.

In the presence of the mitochondrial respiratory chain complex I inhibitor rotenone superoxide production was blocked in diploid neurons, but the increased superoxide generation in Ts16 neurons remained.
32(0,1,1,2) Details
15686486 Clayton R, Clark JB, Sharpe M: Cytochrome c release from rat brain mitochondria is proportional to the mitochondrial functional deficit: implications for apoptosis and neurodegenerative disease. J Biol Chem. 2000 Dec 8;275(49):38581-8.

Titration of rat brain mitochondrial respiratory function, with the specific complex I inhibitor rotenone, caused proportional release of cytochrome c from isolated synaptic and non-synaptic mitochondria.
32(0,1,1,2) Details
18191903 Greene JG, Greenamyre JT, Dingledine R: Sequential and concerted gene expression changes in a chronic in vitro model of parkinsonism. Neurotox Res. 2009 Apr;15(3):260-73. Epub 2009 Feb 24.

To provide a broader perspective on the parkinsonian neurodegenerative process, we have performed a global analysis of gene expression changes caused by chronic, low-level exposure of neuroblastoma cells to the mitochondrial complex I inhibitor and parkinsonian neurotoxin rotenone.
32(0,1,1,2) Details
17149696 Dudimah FD, Odman-Ghazi SO, Hatcher F, Whalen MM: Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: relationship to TBT-induced decreases in NK function. J Appl Toxicol. 2007 Jan-Feb;27(1):86-94.

In this study NK cells were exposed to various concentrations of TBT and to two other compounds that interfere with ATP synthesis (rotenone a complex I inhibitor and oligomycin an ATP synthase inhibitor) for various lengths of time before determining the levels of ATP and lytic function.
31(0,1,1,1) Details
19924288 Xiong N, Huang J, Zhang Z, Zhang Z, Xiong J, Liu X, Jia M, Wang F, Chen C, Cao X, Liang Z, Sun S, Lin Z, Wang T: Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease. Mech Ageing Dev. 1997 Nov;98(2):95-111.

To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra.
31(0,1,1,1) Details
15384065 Zhu C, Vourc'h P, Fernagut PO, Fleming SM, Lacan S, Dicarlo CD, Seaman RL, Chesselet MF: Variable effects of chronic subcutaneous administration of rotenone on striatal histology. J Comp Neurol. 2004 Oct 25;478(4):418-26.

When infused in rats, rotenone, a mitochondrial complex I inhibitor, induces alterations that resemble the histological changes of Parkinson's disease, particularly degeneration of the nigrostriatal dopaminergic system.
31(0,1,1,1) Details
17646711 Kim BJ, Jeon JH, Kim SJ, So I, Kim KW: Regulation of transient receptor potential melastatin 7 (TRPM7) currents by mitochondria. J Neurosci Res. 1999 Jul 15;57(2):195-206.

The respiratory chain complex I inhibitor, rotenone, and complex III inhibitor, antimycin A, were without effect as were kaempferol, an activator of the mitochondrial Ca2+ uniporter, and ruthenium red, an inhibitor of the mitochondrial Ca2+ uniporter.
31(0,1,1,1) Details
19605638 Bao L, Avshalumov MV, Patel JC, Lee CR, Miller EW, Chang CJ, Rice ME: Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling. Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):14-24.

Using direct fluorescence imaging of H (2) O (2) and tissue analysis of ATP, we found that coapplication of rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a complex II substrate, limited H (2) O (2) production, but maintained tissue ATP content.
31(0,1,1,1) Details
19874289 Avila-Gomez IC, Velez-Pardo C, Jimenez-Del-Rio M: Effects of insulin-like growth factor-1 on rotenone-induced apoptosis in human lymphocyte cells. Biochim Biophys Acta. 2006 Dec;1757(12):1568-74. Epub 2006 Sep 29.

The present work shows that rotenone, a mitochondrial complex I inhibitor, induced time- and concentration-dependent apoptosis in lymphocytes which was mediated by anion superoxide radicals (O (2)*(-))/hydrogen peroxide, depolarization of mitochondria, caspase-3 activation, concomitantly with the nuclear translocation of transcription factors such as NF-kappaB, p53, c-Jun and nuclei fragmentation.
31(0,1,1,1) Details
16781463 Guidarelli A, Sciorati C, Clementi E, Cantoni O: Peroxynitrite mobilizes calcium ions from ryanodine-sensitive stores, a process associated with the mitochondrial accumulation of the cation and the enforced formation of species mediating cleavage of genomic DNA. Neurochem Res. 2003 Oct;28(10):1575-81.

These results, along with our previous findings indicating that the DNA damage induced by peroxynitrite is also suppressed by inhibition of the electron flow through complex I, e.g., by rotenone, or by the respiration-deficient phenotype, demonstrate that the mitochondrial formation of DNA-damaging species is critically regulated by the inhibition of complex III and by the availability of Ca (2+).
31(0,1,1,1) Details
12153473 Poppe M, Reimertz C, Munstermann G, Kogel D, Prehn JH: Ceramide-induced apoptosis of D283 medulloblastoma cells requires mitochondrial respiratory chain activity but occurs independently of caspases and is not sensitive to Bcl-xL overexpression. Biochem J. 1987 Nov 1;247(3):657-62.

Treatment with the complex I inhibitor rotenone, C2- or C8-ceramide induced cell death in D283 control cells, while rho- cells were significantly protected.
31(0,1,1,1) Details
12758076 Marques I, Duarte M, Videira A: The 9.8 kDa subunit of complex I, related to bacterial Na (+)-translocating NADH dehydrogenases, is required for enzyme assembly and function in Neurospora crassa. J Appl Physiol. 2000 Jul;89(1):72-80.

Respiration of mutant mitochondria on matrix NADH is rotenone-insensitive, confirming that the 9.8 kDa protein is required for the assembly and activity of complex I.
8(0,0,1,3) Details
8063722 Majander A, Finel M, Wikstrom M: Diphenyleneiodonium inhibits reduction of iron-sulfur clusters in the mitochondrial NADH-ubiquinone oxidoreductase (Complex I). Brain Res Mol Brain Res. 2005 Mar 24;134(1):109-18. Epub 2005 Jan 6.

Similar results were found with Complex I and two rotenone-insensitive preparations, subcomplex I lambda and the flavoprotein fraction.
8(0,0,1,3) Details
8307034 Friedrich T, van Heek P, Leif H, Ohnishi T, Forche E, Kunze B, Jansen R, Trowitzsch-Kienast W, Hofle G, Reichenbach H, et al.: Two binding sites of inhibitors in NADH: ubiquinone oxidoreductase (complex I). Anticancer Drugs. 2009 Oct;20(9):770-8.

Class II inhibitors including the naturally occurring rotenone, phenoxan, aureothin and the synthetic benzimidazole inhibit complex I from all species in an non-competitive manner, but have no effect on the glucose dehydrogenase.
4(0,0,0,4) Details
17060316 O'Malley Y, Fink BD, Ross NC, Prisinzano TE, Sivitz WI: Reactive oxygen and targeted antioxidant administration in endothelial cell mitochondria. J Biol Chem. 2006 Dec 29;281(52):39766-75. Epub 2006 Oct 23.

ROS measured by fluorescence resulted from complex I superoxide released to the matrix and converted to H (2) O (2).
ROS fluorescence by mitochondria fueled by the complex II substrate, succinate, was substantial but markedly inhibited by rotenone.
4(0,0,0,4) Details
8571432 Piantadosi CA, Zhang J: Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. J Neurochem. 2005 May;93(3):526-37.


Salicylic acid was infused into the hippocampus during the experiments, and changes in the recovery of its hydroxylated product, 2,3-dihydroxybenzoic acid (2,3-DHBA), were used to assess the effects of inhibitors of mitochondrial complex I on formation of hydroxyl radical during IR.
3(0,0,0,3) Details
17530440 Liu Y, Qiao DR, Zheng HB, Dai XL, Bai LH, Zeng J, Cao Y: Cloning and sequence analysis of the gene encoding 19-kD subunit of Complex I from Dunaliella salina. FEMS Yeast Res. 2003 Apr;3(2):141-8.

The 19-kD subunit mRNA expression was observed in oxygen deficiency, salt treatment, and rotenone treatment with lower levels.
3(0,0,0,3) Details
18395512 Lambert AJ, Buckingham JA, Boysen HM, Brand MD: Diphenyleneiodonium acutely inhibits reactive oxygen species production by mitochondrial complex I during reverse, but not forward electron transport. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3436-41.

We investigated the effects of diphenyleneiodonium (DPI) on superoxide production by complex I in mitochondria isolated from rat skeletal muscle.
It had no effect on superoxide production during forward electron transport from NAD-linked substrates in the presence of rotenone (to maximise superoxide production from the flavin of complex I) or antimycin (to maximise superoxide production from complex III), suggesting that the effects of DPI were not through inhibition of the flavin.
3(0,0,0,3) Details
3456345 Davies KJ, Doroshow JH: Redox cycling of anthracyclines by cardiac mitochondria. Neurobiol Aging. 2010 Apr;31(4):636-46. Epub 2008 Jul 17.

In the present study we have used beef heart submitochondrial preparations (BH-SMP) to demonstrate that a component of mitochondrial Complex I, probably the NADH dehydrogenase flavin, is the mitochondrial site of anthracycline reduction.
Inhibitor experiments (rotenone, amytal, piericidin A) indicated that the anthracycline reduction site lies on the substrate side of ubiquinone.
2(0,0,0,2) Details
11245784 Joseph-Horne T, Hollomon DW, Wood PM: Fungal respiration: a fusion of standard and alternative components. FEBS Lett. 2010 Mar 5;584(5):883-8. Epub 2010 Jan 13.

These consist of alternative NADH dehydrogenases, which catalyse rotenone insensitive oxidation of matrix NADH or enable cytoplasmic NADH to be used directly.
A few fungi lack Complex I.
2(0,0,0,2) Details
17992568 Ahmadi FA, Grammatopoulos TN, Poczobutt AM, Jones SM, Snell LD, Das M, Zawada WM: Dopamine selectively sensitizes dopaminergic neurons to rotenone-induced apoptosis. Neurochem Res. 2008 May;33(5):886-901. Epub 2007 Nov 10.

Our results demonstrate that an inhibitor of mitochondrial complex I and increased cytosolic DA may cooperatively lead to conditions of elevated oxidative stress and thereby promote selective demise of dopaminergic neurons.
1(0,0,0,1) Details
3005279 Doroshow JH, Davies KJ: Redox cycling of anthracyclines by cardiac mitochondria. J Pharmacol Exp Ther. 1997 Feb;280(2):638-49.

In the presence of rotenone, initial rates of oxygen consumption and superoxide formation were identical under comparable experimental conditions.
Chem. 261, 3060-3067), we have demonstrated that anthracycline antibiotics are reduced to the semiquinone form at Complex I of the mitochondrial electron transport chain.
1(0,0,0,1) Details
11724769 Lee HJ, Shin SY, Choi C, Lee YH, Lee SJ: Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors. Jpn J Cancer Res. 1992 Aug;83(8):899-906.

Treatment with rotenone, an inhibitor of complex I, resulted in an increase of detergent-resistant alpha-synuclein aggregates and a reduction in ATP level.
Treatment with rotenone, an inhibitor of complex I, resulted in an increase of detergent-resistant alpha-synuclein aggregates and a reduction in ATP level.
1(0,0,0,1) Details
16120296 Setterfield K, Williams AJ, Donald J, Thorburn DR, Kirby DM, Trounce I, Christodoulou J: Flow cytometry in the study of mitochondrial respiratory chain disorders. Biochem Pharmacol. 1993 May 25;45(10):2115-22.

Cells were incubated overnight in serum free media, followed by incubation with dihydroethidium with and without rotenone, and then analysed using flow cytometry to measure fluorescence.
The change in fluorescence was significantly lower in four of the six patient cell lines, with a correlation between the activity of complex I and change in fluorescence.
1(0,0,0,1) Details
16029202 Buchheim K, Wessel O, Siegmund H, Schuchmann S, Meierkord H: Processes and components participating in the generation of intrinsic optical signal changes in vitro. Mitochondrion. 2002 May;1(5):437-45.

Rotenone, an inhibitor of mitochondrial complex I, yielded decreased amplitudes of the intrinsic optical signal (27 +/- 7% after 40 min, P < 0.01).
Rotenone, an inhibitor of mitochondrial complex I, yielded decreased amplitudes of the intrinsic optical signal (27 +/- 7% after 40 min, P < 0.01).
1(0,0,0,1) Details
8226801 Ohtsuka T, Nishijima M, Suzuki K, Akamatsu Y: Mitochondrial dysfunction of a cultured Chinese hamster ovary cell mutant deficient in cardiolipin. J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S205-8.

Of the respiratory chain complexes, rotenone-sensitive NADH-ubiquinone reductase (Complex I) was most severely impaired in the mutant, whereas its activity was restored in a revertant of the mutant that had regained the ability to synthesize CL.
81(1,1,1,1) Details
9023274 Kruidering M, Van de Water B, de Heer E, Mulder GJ, Nagelkerke JF: Cisplatin-induced nephrotoxicity in porcine proximal tubular cells: mitochondrial dysfunction by inhibition of complexes I to IV of the respiratory chain. Carcinogenesis. 1989 May;10(5):913-20.

Only N,N'-bis (2-chloroethyl)-N-nitrosourea with rotenone (complex I inhibitor) induced ROS formation, which indicates that inhibition of complex I and inhibition of the GSH-Rd is probably the cause of ROS formation.
81(1,1,1,1) Details
20022987 Tatpati LL, Irving BA, Tom A, Bigelow ML, Klaus K, Short KR, Nair KS: The effect of branched chain amino acids on skeletal muscle mitochondrial function in young and elderly adults. Neurochem Int. 2007 Mar;50(4):601-6. Epub 2007 Jan 18.

Results: In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion.
81(1,1,1,1) Details
17490603 Koopman WJ, Hink MA, Verkaart S, Visch HJ, Smeitink JA, Willems PH: Partial complex I inhibition decreases mitochondrial motility and increases matrix protein diffusion as revealed by fluorescence correlation spectroscopy. Neurochem Int. 2008 Feb;52(3):487-94. Epub 2007 Aug 19.

We previously reported that inhibition of mitochondrial complex I (CI) by rotenone induces marked increases in mitochondrial length and degree of branching, thus revealing a relationship between mitochondrial function and shape.
81(1,1,1,1) Details
17474759 Murai M, Ishihara A, Nishioka T, Yagi T, Miyoshi H: The ND1 subunit constructs the inhibitor binding domain in bovine heart mitochondrial complex I. Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H978-H989. Epub 2008 Jun 20.

A variety of complex I inhibitors such as piericidin A and rotenone efficiently suppressed the specific binding of [125I] TDA to ND1, indicating that they share a common binding domain.
38(0,1,1,8) Details
18197244 Marella M, Seo BB, Nakamaru-Ogiso E, Greenamyre JT, Matsuno-Yagi A, Yagi T: Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson's disease. FEBS Lett. 1999 May 21;451(2):157-61.

In fact, rotenone, a complex I inhibitor, has been used for establishing PD models both in vitro and in vivo.
38(0,1,2,3) Details
17346667 Sgobbo P, Pacelli C, Grattagliano I, Villani G, Cocco T: Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 -mediated oxidative insult in H9C2 myocardial cells. Biochem Biophys Res Commun. 2001 Dec 21;289(5):973-8.

A similar protective effect on mitochondrial respiration could be obtained by pre-treatment of the cells with a sub-saturating amount of rotenone, a complex I inhibitor.
34(0,1,1,4) Details
10747996 Scacco S, Vergari R, Scarpulla RC, Technikova-Dobrova Z, Sardanelli A, Lambo R, Lorusso V, Papa S: cAMP-dependent phosphorylation of the nuclear encoded 18-kDa (IP) subunit of respiratory complex I and activation of the complex in serum-starved mouse fibroblast cultures. J Biol Chem. 2000 Jun 9;275(23):17578-82.

Phosphorylation of the 18-kDa subunit, in response to cholera toxin treatment of fibroblasts, was accompanied by a 2-3-fold enhancement of the rotenone-sensitive endogenous respiration of fibroblasts, of the rotenone-sensitive NADH oxidase, and of the NADH:ubiquinone oxidoreductase activity of complex I.
34(0,1,1,4) Details
17084831 Shinde SB, Save VC, Patil ND, Mishra KP, Tendolkar AG: Impairment of mitochondrial respiratory chain enzyme activities in tetralogy of Fallot. Clin Chim Acta. 2007 Feb;377(1-2):138-43. Epub 2006 Sep 26.

The activities of rotenone-sensitive NADH cytochrome c reductase (complexes I+III), cytochrome c oxidase (complex IV) and the ratio of I and III to II and III complexes (complex I) were significantly lower in TOF (p <0.001).
32(0,1,1,2) Details
17855661 Hsu YC, Lee HC, Ping YH, Liu TY, Lui WY, Chi CW: Mitochondria are an essential mediator of nitric oxide/cyclic guanosine 3',5'-monophosphate blocking of glucose depletion induced cytotoxicity in human HepG2 cells. Mol Biochem Parasitol. 1991 Apr;45(2):185-92.

Furthermore, we found that rotenone and antimycin A (mitochondria complex I and III inhibitors, respectively) blocked SNP cytoprotection against glucose depletion-induced cytotoxicity.
32(0,1,1,2) Details
11971654 Krungkrai J, Kanchanarithisak R, Krungkrai SR, Rochanakij S: Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium berghei. J Mol Biol. 2002 Jun 21;319(5):1211-21.

NADH dehydrogenase of respiratory complex I was demonstrated in isolated mitochondrial organelles of the human parasite Plasmodium falciparum and the mouse parasite Plasmodium berghei by using the specific inhibitor rotenone on oxygen consumption and enzyme activity.
32(0,1,1,2) Details
19074024 Rojas JC, Lee J, John JM, Gonzalez-Lima F: Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy. J Neurosci. 1996 Jun 15;16(12):3807-16.

Subjects were pigmented rats that received single bilateral intravitreal doses of rotenone, a mitochondrial complex I inhibitor, or rotenone plus one of three different doses of NIL.
32(0,1,1,2) Details
19114014 Borland MK, Trimmer PA, Rubinstein JD, Keeney PM, Mohanakumar K, Liu L, Bennett JP Jr: Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells. Bioorg Med Chem. 2010 Feb;18(3):1312-20. Epub 2009 Dec 26.

RESULTS: We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models.
32(0,1,1,2) Details
15371739 Isaev NK, Stelmashook EV, Ruscher K, Andreeva NA, Zorov DB: Menadione reduces rotenone-induced cell death in cerebellar granule neurons. Life Sci. 2003 Nov 7;73(25):3277-88.

Chemical hypoxia (term defining the simulation by using respiratory inhibitors) chosen as in vitro ischemic model, was induced in primary cultures of rat cerebellar granule neurons by inhibitors of mitochondrial electron transport such as rotenone or paraquat (complex I), 3-nitropropionic acid (3-NPA, complex II), antimycin A (complex III), or sodium azide (complex IV).
31(0,1,1,1) Details
8790427 Murphy AN, Bredesen DE, Cortopassi G, Wang E, Fiskum G: Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Biochem J. 1977 Aug 1;165(2):295-301.

This difference was less apparent when respiration was driven by the oxidation of succinate in the presence of the respiratory complex I inhibitor rotenone.
31(0,1,1,1) Details
12603842 Tai KK, McCrossan ZA, Abbott GW: Activation of mitochondrial ATP-sensitive potassium channels increases cell viability against rotenone-induced cell death. J Mol Biol. 2003 May 30;329(2):283-90.

We recently showed that activation of ATP-sensitive potassium (KATP) channels in PC12 cells induces protection against the neurotoxic effect of rotenone, a mitochondrial complex I inhibitor.
31(0,1,1,1) Details
16342116 Koopman WJ, Visch HJ, Smeitink JA, Willems PH: Simultaneous quantitative measurement and automated analysis of mitochondrial morphology, mass, potential, and motility in living human skin fibroblasts. Free Radic Res. 2002 Apr;36(4):421-7.

It was found that acute inhibition of mitochondrial complex I (NADH:ubiquinone oxidoreductase) by means of rotenone transiently reduced mitochondrial branching, area, and potential.
31(0,1,1,1) Details
15964900 Chapman KE, Sinclair SE, Zhuang D, Hassid A, Desai LP, Waters CM: Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. Biochim Biophys Acta. 2001 Apr 2;1504(2-3):173-8.

Rotenone, a mitochondrial complex I inhibitor, partially abrogated the stretch-induced generation of O2- after 2 h CMS in 16HBE cells.
31(0,1,1,1) Details
16663636 Ravanel P, Tissut M, Douce R: Effects of Rotenoids on Isolated Plant Mitochondria. . Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L834-41. Epub 2005 Jun 17.

Then, a one-third decrease of the ADP/O ratio can be measured.Such a selective inhibition of complex I is obtained with deguelin, tephrosin, elliptone, OH-12 rotenone, and almost all the rotenoids extracted from Derris roots.
31(0,1,1,1) Details
8981035 Rao DN, Cederbaum AI: A comparative study of the redox-cycling of a quinone (rifamycin S) and a quinonimine (rifabutin) antibiotic by rat liver microsomes. J Biol Chem. 2001 Mar 23;276(12):9038-44. Epub 2000 Dec 21.

The electron transport chain inhibitors such as rotenone and antimycin A enhanced the signal intensity of DMPO-OH, suggesting NADH dehydrogenase (complex I) as the major component involved in the reduction of rifamycin S.
31(0,1,1,1) Details
17881465 Ding G, Zhang A, Huang S, Pan X, Zhen G, Chen R, Yang T: ANG II induces c-Jun NH2-terminal kinase activation and proliferation of human mesangial cells via redox-sensitive transactivation of the EGFR. Biochem Pharmacol. 1988 Jul 1;37(13):2551-8.

In contrast, inhibitors of other oxidant-producing enzymes, including the mitochondrial complex I inhibitor rotenone, the xanthine oxidase inhibitor allopurinol, the cyclooxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguiaretic acid, the cytochrome P-450 oxygenase inhibitor ketoconazole, and the nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester, were without effect.
31(0,1,1,1) Details
15254374 Herrero A, Barja G: Localization of the site of oxygen radical generation inside the complex I of heart and nonsynaptic brain mammalian mitochondria. Pediatr Neurol. 1998 Oct;19(4):308-12.

The results, taking together, show that rotenone stimulates NADH-supported superoxide generation, confirming that complex I is a source of oxygen radicals in mammals, in general.
8(0,0,1,3) Details
10924899 Zickermann V, Kurki S, Kervinen M, Hassinen I, Finel M: The NADH oxidation domain of complex I: do bacterial and mitochondrial enzymes catalyze ferricyanide reduction similarly?. Biochim Biophys Acta. 2000 Jul 20;1459(1):61-8.

7(0,0,0,7) Details
17017541 Schmidt WJ, Alam M: Controversies on new animal models of Parkinson's disease pro and con: the rotenone model of Parkinson's disease (PD). J Bioenerg Biomembr. 2001 Jun;33(3):233-42.

These results support the hypothesis of an involvement of complex I in PD and render the rotenone model as a suitable experimental model.
7(0,0,1,2) Details
14665431 Feldkamp T, Kribben A, Roeser NF, Senter RA, Kemner S, Venkatachalam MA, Nissim I, Weinberg JM: Preservation of complex I function during hypoxia-reoxygenation-induced mitochondrial injury in proximal tubules. J Neurochem. 2003 Oct;87(2):448-60.

During titration of complex I activity with rotenone, progressive reduction of NAD+ to NADH was detected at > 20% complex I inhibition, but substantial decreases in ATP levels and mitochondrial membrane potential did not occur until > 70% inhibition.
4(0,0,0,4) Details
17055488 Seo BB, Marella M, Yagi T, Matsuno-Yagi A: The single subunit NADH dehydrogenase reduces generation of reactive oxygen species from complex I. FEBS Lett. 2006 Nov 13;580(26):6105-8. Epub 2006 Oct 16.

Incubation of non-transduced cells with rotenone elicited oxidative damage to mitochondrial DNA as well as lipid peroxidation.
4(0,0,0,4) Details
10072046 Carelli V, Ghelli A, Bucchi L, Montagna P, De Negri A, Leuzzi V, Carducci C, Lenaz G, Lugaresi E, Degli Esposti M: Biochemical features of mtDNA 14484 (ND6/M64V) point mutation associated with Leber's hereditary optic neuropathy. Neurochem Int. 2000 May;36(6):489-97.


We report the effect on complex I function of the 14484 Leber's hereditary optic neuropathy (LHON) mutation affecting the ND6 subunit gene.
3(0,0,0,3) Details
11695186 Schuler F, Casida JE: The insecticide target in the PSST subunit of complex I. . Mol Cell Biochem. 1997 Sep;174(1-2):329-33.

3(0,0,0,3) Details
16641458 Biagini GA, Viriyavejakul P, O'neill PM, Bray PG, Ward SA: Functional characterization and target validation of alternative complex I of Plasmodium falciparum mitochondria. Am J Physiol. 1981 Feb;240(2):H308-13.

The inhibitory profile of PfNDH2 revealed that the enzyme activity was insensitive to rotenone, consistent with recent genomic data indicating the absence of the canonical NADH:dehydrogenase enzyme.
3(0,0,0,3) Details
9107311 Darrouzet E, Dupuis A: Genetic evidence for the existence of two quinone related inhibitor binding sites in NADH-CoQ reductase. Ann Neurol. 2004 Nov;56(5):631-41.


Using the NADH-CoQ reductase of Rhodobacter capsulatus as a model for the mitochondrial Complex I, we have for the first time isolated bacterial mutants resistant to piericidin-A, a classical inhibitor of the mitochondrial enzyme.
2(0,0,0,2) Details
16679036 Lopez-Armada MJ, Carames B, Martin MA, Cillero-Pastor B, Lires-Dean M, Fuentes-Boquete I, Arenas J, Blanco FJ: Mitochondrial activity is modulated by TNFalpha and IL-1beta in normal human chondrocyte cells. Biochim Biophys Acta. 1997 Mar 28;1319(1):1-4.

Rotenone, an inhibitor of complex I, caused a significant reduction of the red/green ratio, but it did not reduce the viability of the chondrocytes.
RESULTS: Compared to basal cells, stimulation with TNFalpha (10 ng/ml) and IL-1beta (5 ng/ml) for 48 h significantly decreased the activity of complex I (TNFalpha=35% and IL-1beta=35%) and the production of ATP (TNFalpha=18% and IL-1beta=19%).
2(0,0,0,2) Details
17657281 Panee J, Liu W, Nakamura K, Berry MJ: The responses of HT22 cells to the blockade of mitochondrial complexes and potential protective effect of selenium supplementation. J Neurochem. 2003 Feb;84(3):491-502.


In summary, our results showed that complex I was the major ROS-generating site in HT22 cells.
2(0,0,0,2) Details
9241135 Hasegawa E, Kang D, Sakamoto K, Mitsumoto A, Nagano T, Minakami S, Takeshige K: A Dual Effect of 1-Methyl-4-phenylpyridinium (MPP+ )-Analogs on the Respiratory Chain of Bovine Heart Mitochondria. Arch Biochem Biophys. 1997 Jan 1;337(1):69-74.

The production of superoxide (O- 2 ) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain.
The production of superoxide (O- 2 ) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain.
1(0,0,0,1) Details
10433094 Myers MA, Georgiou HM, Byron S, Esposti MD: Inhibition of mitochondrial oxidative phosphorylation induces hyper-expression of glutamic acid decarboxylase in pancreatic islet cells. Am J Respir Crit Care Med. 2008 Jul 15;178(2):168-79. Epub 2008 Apr 24.


Inhibitors of NADH-ubiquinone oxidoreductase (complex I) seem to be particularly effective in increasing the expression of GAD in both foetal mouse pancreas and HIT-T15 hamster beta cells, especially in the presence of nutrients such as arginine and glucose.
1(0,0,0,1) Details
16087473 Saborido A, Soblechero L, Megias A: Isolated respiring heart mitochondria release reactive oxygen species in states 4 and 3. Free Radic Res. 2005 Sep;39(9):921-31.

As protein concentration was raised in in vitro assays at 37 degrees C, the rate of H2O2 release by rat heart mitochondria supplemented with pyruvate/malate or with succinate (plus rotenone) was shown to increase (0.03-0.15 mg protein/ml), to decrease (0.2-0.5 mg protein/ml) and to be negligible (over 0.5 mg protein/ml).
Consequently, these findings indicate that isolated mitochondria, respiring in vitro under conditions of forward electron transport, release ROS with Complex I- and II-linked substrates in the resting condition (state 4) and when energy demand is maximal (state 3), provided that there is sufficient oxygen dissolved in the medium.
1(0,0,0,1) Details
10878378 Chandel NS, Trzyna WC, McClintock DS, Schumacker PT: Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin. J Immunol. 2000 Jul 15;165(2):1013-21.

Rotenone, an inhibitor of mitochondrial complex I, abolished the increase in ROS signal, the activation of NF-kappa B, and TNF-alpha gene transcription during hypoxia.
Rotenone, an inhibitor of mitochondrial complex I, abolished the increase in ROS signal, the activation of NF-kappa B, and TNF-alpha gene transcription during hypoxia.
1(0,0,0,1) Details
14511122 Gyulkhandanyan AV, Feeney CJ, Pennefather PS: Modulation of mitochondrial membrane potential and reactive oxygen species production by copper in astrocytes. Antimicrob Agents Chemother. 2008 Jan;52(1):164-70. Epub 2007 Oct 22.

Copper sensitized astrocytes to the action of menadione, an intracellular generator of superoxide anion radical, exogenous hydrogen peroxide (H2O2) and rotenone, an inhibitor of mitochondrial electron transport chain complex I.
Copper sensitized astrocytes to the action of menadione, an intracellular generator of superoxide anion radical, exogenous hydrogen peroxide (H2O2) and rotenone, an inhibitor of mitochondrial electron transport chain complex I.
1(0,0,0,1) Details
2590688 Sled' VD, Zinich VN, Kotliar AB: [One- and two-electron reduction of ubiquinone homologs by NADH- dehydrogenase preparations from the mitochondrial respiratory chain]. J Neurosci. 2009 Sep 9;29(36):11257-62.

The mechanism of ubiquinone homologs reduction by different preparations of mitochondrial NADH dehydrogenase: complex I within submitochondrial particles, isolated NADH-ubiquinone oxidoreductase and soluble low molecular weight NADH dehydrogenase, has been investigated.
It has been shown that NADH oxidation via the rotenone-insensitive reaction is associated with one-electron reduction of low molecular weight ubiquinone homologs (Q0, Q1, Q2) to semiquinone with subsequent fast oxidation of the latter by atmospheric oxygen to form a superoxide radical.
1(0,0,0,1) Details
18242195 Del Prete A, Zaccagnino P, Di Paola M, Saltarella M, Oliveros Celis C, Nico B, Santoro G, Lorusso M: Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions. Neurobiol Dis. 2009 May;34(2):357-65. Epub 2009 Feb 20.

The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability.
The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability.
1(0,0,0,1) Details
18836818 Kumar B, Kumar A, Pandey BN, Mishra KP, Hazra B: Role of mitochondrial oxidative stress in the apoptosis induced by diospyrin diethylether in human breast carcinoma (MCF-7) cells. Mol Cell Biochem. 2009 Jan;320(1-2):185-95. Epub 2008 Oct 4.


Experiments using suitable inhibitors also demonstrated that D7 could alter the electron flow in mitochondrial electron transport chain by affecting target (s) between complex I and complex III, and indicated the probable site of D7-induced generation of ROS.
1(0,0,0,1) Details
10904037 Nethery D, Callahan LA, Stofan D, Mattera R, DiMarco A, Supinski G: PLA (2) dependence of diaphragm mitochondrial formation of reactive oxygen species. Biochim Biophys Acta. 2009 May;1787(5):384-92. Epub 2008 Nov 14.


We also found that administration of arachidonic acid (the principal metabolic product of PLA (2) activation) increased mitochondrial H (2) O (2) formation by interacting with complex I of the electron transport chain.
1(0,0,0,1) Details
16579629 Mirzaei H, Schieler JL, Rochet JC, Regnier F: Identification of rotenone-induced modifications in alpha-synuclein using affinity pull-down and tandem mass spectrometry. Exp Neurol. 2007 Nov;208(1):120-6. Epub 2007 Aug 22.

Using this method, we mapped posttranslational modifications of alpha-synuclein from untreated neurons and neurons exposed to rotenone, an inhibitor of mitochondrial complex I.
1(0,0,0,1) Details
12632423 Maneiro E, Martin MA, de Andres MC, Lopez-Armada MJ, Fernandez-Sueiro JL, del Hoyo P, Galdo F, Arenas J, Blanco FJ: Mitochondrial respiratory activity is altered in osteoarthritic human articular chondrocytes. Arch Biochem Biophys. 1999 Sep 1;369(1):119-26.

The activities of mitochondrial respiratory chain complexes (complex I: rotenone-sensitive NADH-coenzyme Q (1) reductase; complex II: succinate dehydrogenase; complex III: antimycin-sensitive ubiquinol cytochrome c reductase; and complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from OA and normal cartilage.
81(1,1,1,1) Details
18850458 Hayworth CR, Rojas JC, Gonzalez-Lima F: Transgenic mice expressing cyan fluorescent protein as a reporter strain to detect the effects of rotenone toxicity on retinal ganglion cells. Exp Neurol. 2010 Jan;221(1):217-24. Epub 2009 Nov 11.

Rotenone is a widely used pesticide that inhibits mitochondrial complex I and produces neurotoxicity.
81(1,1,1,1) Details
12867501 Gao HM, Liu B, Hong JS: Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. Biochim Biophys Acta. 2010 Mar;1800(3):275-81. Epub 2009 Sep 23.

Mechanistically, rotenone-induced dopaminergic neurodegeneration has been associated with both its inhibition of neuronal mitochondrial complex I and the enhancement of activated microglia.
81(1,1,1,1) Details
11225736 Li YP, Atkins CM, Sweatt JD, Reid MB: Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes. Biochem Int. 1986 Aug;13(2):351-7.

We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain.
81(1,1,1,1) Details
16402917 Reinecke F, Levanets O, Olivier Y, Louw R, Semete B, Grobler A, Hidalgo J, Smeitink J, Olckers A, Van der Westhuizen FH: Metallothionein isoform 2A expression is inducible and protects against ROS-mediated cell death in rotenone-treated HeLa cells. J Hypertens. 2006 Apr;24(4):757-66.

HeLa cells were titrated with rotenone, resulting in dose-dependent decrease in complex I activity and elevated ROS production at activities lower than 33%.
38(0,1,2,3) Details
9593947 Lummen P: Complex I inhibitors as insecticides and acaricides. Biochem Pharmacol. 1991 Mar 1;41(5):677-84.

Mechanistic studies indicated that these compounds interfered with ubiquinone reduction most likely at the same site (s) as the classical complex I inhibitors rotenone and piericidin A.
37(0,1,1,7) Details
16887699 Woznica A, Dzirba J, Manka D, Labuzek S: Effects of electron transport inhibitors on iron reduction in Aeromonas hydrophila strain KB1. Anaerobe. 2003 Jun;9(3):125-30.

The observed inhibition of iron reduction by rotenone and capsaicin may suggest the existence of Q sites in formate reductase, analogous to those in complex I.
37(0,1,2,2) Details
9824162 Higuchi M, Proske RJ, Yeh ET: Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Life Sci. 2006 May 15;78(25):2889-97. Epub 2005 Dec 27.

This hypothesis is supported by the following observations: (1) TNF and rotenone induced MPT and cytochrome c release; (2) TNF-induced complex I inhibition was observed prior to cytochrome c release and MPT induction; (3) MPT induction was inhibited by a caspase 3 inhibitor, z-DEVD-CH2F, and an antioxidant pyrrolidine dithiocarbamate (PDTC), whereas cytochrome c release was only inhibited by PDTC.
35(0,1,1,5) Details
1959619 Majander A, Huoponen K, Savontaus ML, Nikoskelainen E, Wikstrom M: Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON). Arch Biochem Biophys. 1992 Sep;297(2):253-7.

The ND1/3460 mutation exhibits 80% reduction in rotenone-sensitive and ubiquinone-dependent electron transfer activity, whereas the proximal NADH dehydrogenase activity of the Complex is unaffected.
34(0,1,1,4) Details
9449419 Seaton TA, Cooper JM, Schapira AH: Free radical scavengers protect dopaminergic cell lines from apoptosis induced by complex I inhibitors. Biochemistry. 1992 Nov 24;31(46):11413-9.

We have demonstrated that complex I inhibitors, including rotenone, MPP+, isoquinoline and tetrahydroisoquinoline, induce apoptosis in PC12 and SK-N-MC dopaminergic cell lines which was decreased by pretreatment with N-acetylcysteine, TEMPO, dihydrolipoic acid or pyrrolidine dithiocarbamate.
34(0,1,1,4) Details
12558969 Hoglinger GU, Feger J, Prigent A, Michel PP, Parain K, Champy P, Ruberg M, Oertel WH, Hirsch EC: Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. Mol Carcinog. 2010 Feb;49(2):141-51.

Male Lewis rats infused with rotenone, a lipophilic complex I inhibitor [2.5 mg/kg/day intraveneously (i.v.) for 28 days], were compared with vehicle-infused controls.
34(0,1,1,4) Details
7945357 Sivan VM, Raj RK: Lactate oxidation coupled to energy production in mitochondria like particles from Setaria digitata, a filarial parasite. Biochem Biophys Res Commun. 1994 Oct 14;204(1):17-22.

The ferricyanide reduction by lactate is found to be sensitive to the cytochrome o inhibitor orthohydroxy diphenyl (OHD) and complex I inhibitor rotenone, modulated by ADP (+) and ATP (-) and inhibited by pyruvate and oxaloacetate.
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12062197 Agani FH, Pichiule P, Carlos Chavez J, LaManna JC: Inhibitors of mitochondrial complex I attenuate the accumulation of hypoxia-inducible factor-1 during hypoxia in Hep3B cells. Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1312-9.

Because mitochondria have been postulated to be involved in the regulation of HIF-1, we tested the effects of mitochondrial electron transport chain complex I inhibitors, rotenone and 1-methyl-4-phenylpiridinium (MPP (+)), on hypoxic-induced accumulation of HIF-1 alpha, the regulated component of the dimer.
32(0,1,1,2) Details
15590775 Melo AM, Bandeiras TM, Teixeira M: New insights into type II NAD (P) H:quinone oxidoreductases. Biochim Biophys Acta. 2006 May-Jun;1757(5-6):525-34. Epub 2006 Apr 7.

However, they have the common feature of being resistant to the complex I classical inhibitors rotenone, capsaicin, and piericidin A.
32(0,1,1,2) Details
1787040 Mendis AH, Armson A, Thompson RC, Grubb WB: The response of intact Strongyloides ratti infective (L3) larvae to substrates and inhibitors of respiratory electron transport. Microbiol Mol Biol Rev. 2004 Dec;68(4):603-16.

Respiratory electron transport (RET) Complex I inhibitor rotenone (2 microM) produced 33 +/- 6.5% inhibition of the E-QO2.
31(0,1,1,1) Details
6745260 Cook ND, Cammack R: Purification and characterization of the rotenone-insensitive NADH dehydrogenase of mitochondria from Arum maculatum. Biochem Mol Med. 1996 Dec;59(2):134-7.

Affinity chromatography on 5'-ADP-Sepharose 4B was used to separate the rotenone-sensitive (complex I) NADH dehydrogenase from the rotenone-insensitive NADH dehydrogenase.
31(0,1,1,1) Details
11198300 Lotharius J, O'Malley KL: Role of mitochondrial dysfunction and dopamine-dependent oxidative stress in amphetamine-induced toxicity. Ann Neurol. 2001 Jan;49(1):79-89.

In contrast, when primary cultures of dopaminergic neurons were exposed to AMPH in the presence of subtoxic doses of the mitochondrial complex I inhibitor rotenone, cell death was dramatically increased, mimicking the effects of a known parkinsonism-inducing toxin.
31(0,1,1,1) Details
15223368 Kanki R, Nakamizo T, Yamashita H, Kihara T, Sawada H, Uemura K, Kawamata J, Shibasaki H, Akaike A, Shimohama S: Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons. Cytometry A. 2006 Jan;69(1):1-12.

We investigated the relationship between glutamate excitotoxicity and mitochondrial dysfunction elicited by rotenone (a complex I inhibitor), malonate (a complex II inhibitor), or antimycin (a complex III inhibitor), in primary cultures of the embryonic rat spinal cord.
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7999034 Pecci L, Fontana M, Montefoschi G, Cavallini D: Aminoethylcysteine ketimine decarboxylated dimer protects submitochondrial particles from lipid peroxidation at a concentration not inhibitory of electron transport. Mol Cell Endocrinol. 2000 Oct 25;168(1-2):127-34.

Furthermore the dimer is able to counteract the malondialdehyde formation stimulated by the Complex I inhibitors rotenone and N-methyl-4-phenylpyridinium (MPP+).
31(0,1,1,1) Details
7959172 Rembish SJ, Trush MA: Further evidence that lucigenin-derived chemiluminescence monitors mitochondrial superoxide generation in rat alveolar macrophages. Am J Physiol Renal Physiol. 2007 Dec;293(6):F1889-97. Epub 2007 Sep 19.

The agents examined included a Complex I inhibitor, rotenone; a Complex III inhibitor, antimycin a; and a Complex IV inhibitor, KCN.
31(0,1,1,1) Details
19384599 Rojas JC, John JM, Lee J, Gonzalez-Lima F: Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy. Neuroreport. 2002 Jul 19;13(10):1279-83.

Methylene blue (MB) is a diaminophenothiazine with potent antioxidant and unique redox properties that prevent morphologic degenerative changes in the mouse retina induced by rotenone, a specific mitochondrial complex I inhibitor.
31(0,1,1,1) Details
17123556 Leung KW, Yung KK, Mak NK, Chan YS, Fan TP, Wong RN: Neuroprotective effects of ginsenoside-Rg1 in primary nigral neurons against rotenone toxicity. Biochem Biophys Res Commun. 1993 Oct 15;196(1):355-62.

Rotenone, a common household pesticide known for its specific and irreversible mitochondria complex I inhibition, has been suggested to be the causal agent of Parkinson's disease (PD) by inducing degeneration of cells in the substantial nigra.
31(0,1,1,1) Details
9915790 Okun JG, Lummen P, Brandt U: Three classes of inhibitors share a common binding domain in mitochondrial complex I (NADH:ubiquinone oxidoreductase). J Physiol. 1997 Oct 1;504 ( Pt 1):175-89.

Although the rotenone site overlaps with both the piericidin A and the capsaicin site, the latter two sites do not overlap.
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3178753 Cottingham IR, Moore AL: Analysis of NADH dehydrogenases from plant [mung bean (Phaseolus aureus)] mitochondrial membranes on non-denaturing polyacrylamide gels and purification of complex I by band excision. Biochemistry. 1994 Aug 16;33(32):9675-83.

A rotenone-sensitive NADH dehydrogenase (Complex I) was identified on the basis of co-migration with the purified mammalian enzyme.
7(0,0,1,2) Details
12566073 Fang J, Beattie DS: External alternative NADH dehydrogenase of Saccharomyces cerevisiae: a potential source of superoxide. Biochem J. 1979 Apr 15;180(1):129-35.

Three rotenone-insensitive NADH dehydrogenases are present in the mitochondria of yeast Saccharomyces cerevisiae, which lack complex I.
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18486594 Fendel U, Tocilescu MA, Kerscher S, Brandt U: Exploring the inhibitor binding pocket of respiratory complex I. . Biochem Biophys Res Commun. 1994 Mar 15;199(2):755-60.

Many mutations around the domain of the 49-kDa subunit that is homologous to the [NiFe] centre binding region of hydrogenase conferred resistance to DQA (class I/type A) and rotenone (class II/type B) indicating a wider overlap of the binding sites for these two types of inhibitors.
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8439309 Degli Esposti M, Ghelli A, Crimi M, Estornell E, Fato R, Lenaz G: Complex I and complex III of mitochondria have common inhibitors acting as ubiquinone antagonists. Histochem J. 2000 Mar;32(3):133-7.

The stigmatellin analog is more powerful than its parent compound and is noncompetitive with exogenous ubiquinones, rotenone and piericidin.
4(0,0,0,4) Details
8068645 Ahmed I, Krishnamoorthy G: Probing of coenzyme quinone binding site of mitochondrial NADH:CoQ reductase by fluorescence dynamics. Neurochem Int. 2000 May;36(6):483-8.

The coenzyme quinone (CoQ) binding region of mitochondrial NADH:CoQ reductase (complex-I) was investigated by the fluorescent probes erythrosine-5'-iodoacetamide (ER) and 3,3'-diethyloxadicarbocyanine iodide (DODCI).
Binding of the probes was not affected by the binding of the inhibitor rotenone.
4(0,0,0,4) Details
9795106 Seaton TA, Cooper JM, Schapira AH: Cyclosporin inhibition of apoptosis induced by mitochondrial complex I toxins. Exp Neurol. 2009 Jul;218(1):154-61. Epub 2009 May 3.

The present study using propidium iodide and FITC-TUNEL staining to identify apoptotic cells, demonstrates that rotenone, MPP+ and tetrahydroisoquinoline induce apoptosis in PC12 cells.
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9030267 Glinn MA, Lee CP, Ernster L: Pro- and anti-oxidant activities of the mitochondrial respiratory chain: factors influencing NAD (P) H-induced lipid peroxidation. J Biol Chem. 1998 Jun 5;273(23):14210-7.

This paper is a study of factors influencing the rate of lipid peroxidation in beef heart submitochondrial particles induced by NAD (P) H via the NADH-ubiquinone oxidoreductase (Complex I) of the respiratory chain.
Rotenone did not eliminate the biphasicity of the NADH-induced reaction, indicating that this was not due to an antioxidant effect of reduced ubiquinone at high NADH concentrations.
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17263793 Tretter L, Takacs K, Hegedus V, Adam-Vizi V: Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria. Biochemistry. 1998 Aug 25;37(34):11792-6.

H (2) O (2) formation and the increase in NAD (P) H level were inhibited by rotenone, ADP or FCCP, respectively, being consistent with a reverse electron transfer (RET).
We suggest that the metabolism of alpha-GP leads to ROS generation primarily by complex I in RET, and in addition a significant ROS formation could be ascribed to alpha-GP-dehydrogenase in mammalian brain mitochondria.
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8630091 McNaught KS, Thull U, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD: Effects of isoquinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mitochondrial respiration. Brain Res. 2001 Feb 9;891(1-2):94-105.

Isoquinoline derivatives exert 1-methyl-4-phenylpyridinium (MPP+)-like activity as inhibitors of complex I and alpha-ketoglutarate dehydrogenase activity in rat brain mitochondrial fragments.
None of the compounds examined inhibited respiration supported by either succinate + rotenone or tetramethylparaphenylenediamine (TMPD) + ascorbate.
2(0,0,0,2) Details
12556227 Duarte M, Peters M, Schulte U, Videira A: The internal alternative NADH dehydrogenase of Neurospora crassa mitochondria. Toxicology. 2005 Dec;216(1):9-14. Epub 2005 Aug 22.

The respiratory activity of mitochondria from the resulting null-mutant ndi1 is almost fully inhibited by rotenone, an inhibitor of the proton-pumping complex I, when matrix-generated NADH is used as substrate.
The respiratory activity of mitochondria from the resulting null-mutant ndi1 is almost fully inhibited by rotenone, an inhibitor of the proton-pumping complex I, when matrix-generated NADH is used as substrate.
2(0,0,0,2) Details
9395404 Hasegawa E, Kang D, Sakamoto K, Mitsumoto A, Nagano T, Minakami S, Takeshige K: A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-analogs on the respiratory chain of bovine heart mitochondria. Exp Brain Res. 2007 Aug;181(3):435-46. Epub 2007 Apr 12.

The production of superoxide (O2-) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain.
The production of superoxide (O2-) induced by MPP+ or analog 8 was to the same extent as that by rotenone, an inhibitor of complex I of the mitochondrial respiratory chain.
1(0,0,0,1) Details
19763263 Johnson F, Kaplitt MG: Novel mitochondrial substrates of omi indicate a new regulatory role in neurodegenerative disorders. Biochem J. 2006 Dec 15;400(3):541-50.

Additionally our gene expression studies, using rotenone (an inhibitor of Complex I) showed Omi expression was silenced when pdhb and idh3a were increased when a sub-lethal dose was applied.
Additionally our gene expression studies, using rotenone (an inhibitor of Complex I) showed Omi expression was silenced when pdhb and idh3a were increased when a sub-lethal dose was applied.
1(0,0,0,1) Details
19492085 Sandebring A, Thomas KJ, Beilina A, van der Brug M, Cleland MM, Ahmad R, Miller DW, Zambrano I, Cowburn RF, Behbahani H, Cedazo-Minguez A, Cookson MR: Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1. Biochem Pharmacol. 1993 Feb 9;45(3):691-6.

As in previous studies, PINK1 deficient cells have lower mitochondrial membrane potential and are more sensitive to the toxic effects of mitochondrial complex I inhibitors.
We also show that wild-type PINK1, but not recessive mutant or kinase dead versions, protects against rotenone-induced mitochondrial fragmentation whereas PINK1 deficient cells show lower mitochondrial connectivity.
1(0,0,0,1) Details
7670095 Macho A, Castedo M, Marchetti P, Aguilar JJ, Decaudin D, Zamzami N, Girard PM, Uriel J, Kroemer G: Mitochondrial dysfunctions in circulating T lymphocytes from human immunodeficiency virus-1 carriers. Parasitol Res. 2004 Mar;92(4):341-6. Epub 2004 Jan 16.

Control experiments involving rotenone, an inhibitor of the respiratory chain complex I, indicate that the reactive oxygen species responsible for HE --> Eth conversion is generated during mitochondrial electron transport.
Control experiments involving rotenone, an inhibitor of the respiratory chain complex I, indicate that the reactive oxygen species responsible for HE --> Eth conversion is generated during mitochondrial electron transport.
1(0,0,0,1) Details
11479321 Bai Y, Hajek P, Chomyn A, Chan E, Seo BB, Matsuno-Yagi A, Yagi T, Attardi G: Lack of complex I activity in human cells carrying a mutation in MtDNA-encoded ND4 subunit is corrected by the Saccharomyces cerevisiae NADH-quinone oxidoreductase (NDI1) gene. Physiol Behav. 2004 Dec 15;83(3):395-400.

The gene for the single subunit, rotenone-insensitive, and flavone-sensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1) can completely restore the NADH dehydrogenase activity in mutant human cells that lack the essential mitochondrial DNA (mtDNA)-encoded subunit ND4.
1(0,0,0,1) Details
9417880 Guidarelli A, Brambilla L, Clementi E, Sciorati C, Cantoni O: Stimulation of oxygen consumption promotes mitochondrial calcium accumulation, a process associated with, and causally linked to, enhanced formation of tert-butylhydroperoxide-induced DNA single-strand breaks. Exp Cell Res. 1997 Nov 25;237(1):176-85.

A cause-effect relationship between these two parameters was established by showing that: (a) rotenone, an inhibitor of complex I, abolished respiration and prevented the enhancement of the DNA-damaging response under all the above circumstances; (b) the membrane-impermeant, complex I-activating substrate L-malate gave similar results in permeabilized cells; and (c) none of the NADH-linked substrates affected the DNA-damaging response to tert-butylhydroperoxide in respiration-deficient cells.
A cause-effect relationship between these two parameters was established by showing that: (a) rotenone, an inhibitor of complex I, abolished respiration and prevented the enhancement of the DNA-damaging response under all the above circumstances; (b) the membrane-impermeant, complex I-activating substrate L-malate gave similar results in permeabilized cells; and (c) none of the NADH-linked substrates affected the DNA-damaging response to tert-butylhydroperoxide in respiration-deficient cells.
1(0,0,0,1) Details
14561532 Tada-Oikawa S, Hiraku Y, Kawanishi M, Kawanishi S: Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis. Mitochondrion. 2004 Sep;4(5-6):387-94. Epub 2004 Nov 2.

Rotenone, an inhibitor of NADH dehydrogenase complex, is a naturally occurring insecticide, which is capable of inducing apoptosis.
1(0,0,0,1) Details
15342361 Beretta S, Mattavelli L, Sala G, Tremolizzo L, Schapira AH, Martinuzzi A, Carelli V, Ferrarese C: Leber hereditary optic neuropathy mtDNA mutations disrupt glutamate transport in cybrid cell lines. Pediatr Res. 1989 Feb;25(2):194-201.


Three pathogenic mutations (positions 11778/ND4, 3460/ND1 and 14484/ND6) account for the majority of LHON cases and they affect genes that encode for different subunits of mitochondrial complex I.
1(0,0,0,1) Details
18036194 Milusheva E, Baranyi M, Kittel A, Fekete A, Zelles T, Vizi ES, Sperlagh B: Modulation of dopaminergic neurotransmission in rat striatum upon in vitro and in vivo diclofenac treatment. Mol Cells. 2007 Jun 30;23(3):363-9.

In conclusion, whereas in vitro DCF pre-treatment resembles the effect of the mitochondrial toxin rotenone, in vivo it rather counteracts than aggravates dopaminergic dysfunction.
As it is known that selective mitochondrial complex I inhibition combined with mild oxidative stress causes striatal dopaminergic dysfunction, we tested whether DCF also compromise dopaminergic function in the striatum. [3H] Dopamine ([3H] DA) release was measured from rat striatal slices after in vitro (2 h, 10-25 micromol/L) or in vivo (3 mg/kg i.v. for 28 days) DCF treatment.
1(0,0,0,1) Details
12950736 Dell'Anna ML, Urbanelli S, Mastrofrancesco A, Camera E, Iacovelli P, Leone G, Manini P, D'Ischia M, Picardo M: Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients. Free Radic Biol Med. 2004 Jan 1;36(1):16-26.


Moreover, a marked increase in the expression of mitochondrial malate dehydrogenase activity and a specific sensitivity to electron transport chain complex I inhibitor were observed.
1(0,0,0,1) Details
11961005 Morigi M, Macconi D, Zoja C, Donadelli R, Buelli S, Zanchi C, Ghilardi M, Remuzzi G: Protein overload-induced NF-kappaB activation in proximal tubular cells requires H (2) O (2) through a PKC-dependent pathway. J Toxicol Environ Health A. 2008;71(24):1582-92.

To identify the enzymatic sources responsible for the increased H (2) O (2) production, the effect of dyphenyleneiodonium, an inhibitor of the membrane NADP (H) oxidase, was studied, as was the effect of rotenone, which blocks complex I of the mitochondrial respiratory chain.
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16972982 Liu L, Li Y, Li H, Chen J: Significant increase of glycolytic flux in Torulopsis glabrata by inhibition of oxidative phosphorylation. Am J Physiol Heart Circ Physiol. 2009 Jan;296(1):H226-32. Epub 2008 Nov 21.

One was separately adding, at 10 mg L1, specific inhibitors of complex I (rotenone) or of the bc1 complex (antimycin A) to the culture broth of T. glabrata CCTCC M202019, which resulted in significantly decreased intracellular ATP levels (43% and 27.7%) and significantly increased rates of glucose consumption (qs) and pyruvate production (qp); another approach was breeding a respiratory-deficient mutant RD-16, in which cytochromes aa3 and b in the ETC were deleted after ethidium bromide mutagenesis, to reduce the ETC activity constitutively.
81(1,1,1,1) Details
19504041 Pienaar IS, Schallert T, Hattingh S, Daniels WM: Behavioral and quantitative mitochondrial proteome analyses of the effects of simvastatin: implications for models of neural degeneration. J Neurochem. 2007 Feb;100(3):650-63.

Rats were pre-treated with simvastatin for 14 days, followed by a single unihemispheric (substantia nigra; SN) injection of rotenone, a mitochondrial complex I (Co-I) inhibitor.
81(1,1,1,1) Details
15114628 Shavali S, Carlson EC, Swinscoe JC, Ebadi M: 1-Benzyl-1,2,3,4-tetrahydroisoquinoline, a Parkinsonism-inducing endogenous toxin, increases alpha-synuclein expression and causes nuclear damage in human dopaminergic cells. Int J Biochem Cell Biol. 2008;40(9):1792-805. Epub 2008 Jan 19.

Inhibition of complex I by rotenone and depletion of glutathione by L-buthionine sulfoxamine also correlated with an increase in alpha-syn expression, suggesting that oxidative stress may cause an increase in alpha-syn levels in dopaminergic cells.
81(1,1,1,1) Details
14645467 Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT: Mechanism of toxicity in rotenone models of Parkinson's disease. J Cell Sci. 2007 Dec 1;120(Pt 23):4155-66.

Exposure of rats to the pesticide and complex I inhibitor rotenone reproduces features of Parkinson's disease, including selective nigrostriatal dopaminergic degeneration and alpha-synuclein-positive cytoplasmic inclusions (Betarbet et al., 2000; Sherer et al., 2003).
37(0,1,2,2) Details
10354494 Seo BB, Matsuno-Yagi A, Yagi T: Modulation of oxidative phosphorylation of human kidney 293 cells by transfection with the internal rotenone-insensitive NADH-quinone oxidoreductase (NDI1) gene of Saccharomyces cerevisiae. Biochim Biophys Acta. 1991 Oct 18;1060(2):203-9.

The NDI1-transfected HEK 293 cells were able to grow in media containing a complex I inhibitor such as rotenone and 1-methyl-4-phenylpyridinium ion.
37(0,1,2,2) Details
15469939 Kweon GR, Marks JD, Krencik R, Leung EH, Schumacker PT, Hyland K, Kang UJ: Distinct mechanisms of neurodegeneration induced by chronic complex I inhibition in dopaminergic and non-dopaminergic cells. J Neurochem. 2002 Oct;83(1):220-8.

To elucidate the mechanisms of chronic complex I disruption-induced neurodegeneration, we induced differentiation of immortalized midbrain dopaminergic (MN9D) and non-dopaminergic (MN9X) neuronal cells, to maintain them in culture without significant cell proliferation and compared their survivals following chronic exposure to nanomolar rotenone, an irreversible complex I inhibitor.
34(0,1,1,4) Details
3094534 Suzuki H, Wakai M, Ozawa T: Selective inhibition of mitochondrial NADH-ubiquinone reductase (Complex I) by an alkyl polyoxyethylene ether. J Appl Physiol. 2008 Oct;105(4):1114-26. Epub 2008 Aug 14.

Partial removal of phospholipids from Complex I from 18.8% (w/w) to 14.5% significantly decreased its susceptibility to the inhibitor as well as to rotenone.
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8806050 Sablin SO, Krueger MJ, Yankovskaya VL, Tkachenko SE, Razdolsky AN, Bachurin SO, Ramsay RR, Singer TP: Inhibition of NADH oxidation by 1-methyl-4-phenylpyridinium analogs as the basis for the prediction of the inhibitory potency of novel compounds. J Biochem Toxicol. 1996;11(1):33-43.

The IC50 values for these compounds and previously published figures for MPP+ analogs were then used to select a computer model based on structural parameters to predict the inhibitory potency of other compounds that react at the "rotenone site" in Complex I.
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17854275 Doughan AK, Dikalov SI: Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis. Biochim Biophys Acta. 1997 Jul 4;1320(3):256-64.

Inhibitor analysis suggested that the redox cycling of MitoQ occurred at two sites on complex I, proximal and distal to the rotenone-binding site.
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20064719 Geldenhuys WJ, Funk MO, Barnes KF, Carroll RT: Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET. Bioorg Med Chem Lett. 2010 Feb 1;20(3):819-23. Epub 2010 Jan 4.

To investigate the ability of NL-1 to block rotenone initiated free radicals from complex I, we found it was able to protect the human neuronal cell line SH-SY5Y against rotenone induced cell death.
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19339632 Huang S, Zhang A, Ding G, Chen R: Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation. Am J Physiol Renal Physiol. 2009 Jun;296(6):F1323-33. Epub 2009 Apr 1.

Pretreatment with the antioxidant N-acetyl-l-cysteine, catalase, SOD, mitochondrial respiratory chain complex I inhibitor rotenone (Rot), NADPH oxidase inhibitor apocynin, and DPI significantly inhibited Aldo-stimulated MC proliferation as well as EGFR transactivation.
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16668549 Luethy MH, Hayes MK, Elthon TE: Partial Purification and Characterization of Three NAD (P) H Dehydrogenases from Beta vulgaris Mitochondria. Plant Physiol. 1991 Dec;97(4):1317-1322.

All three peaks are insensitive to divalent cation chelators and a complex I inhibitor, rotenone.
31(0,1,1,1) Details
9586799 Tsai MJ, Lee EH: Nitric oxide donors protect cultured rat astrocytes from 1-methyl-4-phenylpyridinium-induced toxicity. Free Radic Biol Med. 1998 Mar 15;24(5):705-13.

NO. donors and analogues were also tested against damage produced by rotenone, an irreversible complex I inhibitor.
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17207576 Thompson RJ, Buttigieg J, Zhang M, Nurse CA: A rotenone-sensitive site and H2O2 are key components of hypoxia-sensing in neonatal rat adrenomedullary chromaffin cells. J Neurol Sci. 2005 May 15;232(1-2):95-103.

Of several mitochondrial electron transport chain (ETC) inhibitors tested, only rotenone, a complex I blocker, mimicked and occluded the effects of hypoxia on outward current, cellular ROS, and ATP secretion.
31(0,1,1,1) Details
17673201 Tozzi A, Costa C, Di Filippo M, Tantucci M, Siliquini S, Belcastro V, Parnetti L, Picconi B, Calabresi P: Memantine reduces neuronal dysfunctions triggered by in vitro ischemia and 3-nitropropionic acid. Biochim Biophys Acta. 2010 Feb 17.

Moreover, memantine showed protection against irreversible field potential loss induced by 3-nitropropionic acid (3-NP), an inhibitor of the mitochondrial complex II, without influencing toxicity induced by rotenone, a complex I inhibitor.
31(0,1,1,1) Details
15794752 Falchi AM, Isola R, Diana A, Putzolu M, Diaz G: Characterization of depolarization and repolarization phases of mitochondrial membrane potential fluctuations induced by tetramethylrhodamine methyl ester photoactivation. Biochem J. 2003 May 1;371(Pt 3):1005-11.

The frequency of R phases was significantly inhibited by oligomycin and aurovertin (mitochondrial ATP synthase inhibitors), rotenone (mitochondrial complex I inhibitor) and iodoacetic acid (inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase).
31(0,1,1,1) Details
8078526 Beattie DS, Obungu VH, Kiaira JK: Oxidation of NADH by a rotenone and antimycin-sensitive pathway in the mitochondrion of procyclic Trypanosoma brucei brucei. Biochem Biophys Res Commun. 1994 Nov 30;205(1):264-8.

Both NADH:cytochrome c and NADH:ubiquinone reductase activities were inhibited 80-90% by rotenone indicating the presence of a complex I-like NADH dehydrogenase in the mitochondrion of trypanosomes.
31(0,1,1,1) Details
11909981 Schapira AH: Neuroprotection and dopamine agonists. . J Physiol. 2003 May 1;548(Pt 3):789-800. Epub 2003 Mar 7.

Neuronal toxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce parkinsonism in human and animal models, and rotenone, another specific mitochondrial complex I inhibitor, can induce similar effects in rodents to produce a model for PD.
31(0,1,1,1) Details
15992782 Sindhu KM, Saravanan KS, Mohanakumar KP: Behavioral differences in a rotenone-induced hemiparkinsonian rat model developed following intranigral or median forebrain bundle infusion. J Biol Chem. 1997 Apr 11;272(15):9605-8.

A mitochondrial complex-I inhibitor, rotenone was unilaterally infused into the substantia nigra pars compacta (SNpc) or median forebrain bundle (MFB) to create hemiparkinsonian animal models and investigated spontaneous and drug-induced stereotypic rotations, as well as certain postural behaviors in Sprague-Dawley rats.
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11728422 Yuki K, Suzuki T, Katoh S, Kakinuma Y, Miyauchi T, Mitsui Y: Endothelin-1 stimulates cardiomyocyte injury during mitochondrial dysfunction in culture. Int J Biochem Cell Biol. 2008;40(10):2098-109. Epub 2008 Feb 16.

Primary cultured cardiomyocytes from neonatal rats were pretreated with rotenone, a mitochondrial complex I inhibitor, and the cytotoxic effect of endothelin-1 on the cardiomyocytes was demonstrated.
31(0,1,1,1) Details
3110216 Hoppel CL, Kerr DS, Dahms B, Roessmann U: Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Biol Bull. 2007 Apr;212(2):169-75.

Mitochondrial NADH dehydrogenase activity (complex I, assayed as rotenone-sensitive NADH oxidase, NADH-duroquinone reductase, and NADH-cytochrome c reductase) was 0-10% of controls, and NADH-ferricyanide reductase activity was 25-50% of controls in the mitochondria and in skin fibroblasts.
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8192914 Birch-Machin MA, Briggs HL, Saborido AA, Bindoff LA, Turnbull DM: An evaluation of the measurement of the activities of complexes I-IV in the respiratory chain of human skeletal muscle mitochondria. Int Immunol. 1997 Jun;9(6):835-41.

Complex I activity is measured in the presence of 2.5 mg.ml-1 bovine serum albumin, which increases rotenone sensitivity, and we have shown that NADH-cytochrome b5 reductase makes an important contribution to the rotenone-insensitive NADH-ubiquinone oxidoreductase activity.
7(0,0,1,2) Details
6460022 Schwitzguebel JP, Palmer JM: Properties of mitochondria as a function of the growth stages of Neurospora crassa. Anal Biochem. 1995 Sep 1;230(1):16-9.

One pathway was sensitive to rotenone and involved three energy-coupling sites, whereas the other was resistant to rotenone and bypassed complex I.
7(0,0,1,2) Details
14670598 Grivennikova VG, Roth R, Zakharova NV, Hagerhall C, Vinogradov AD: The mitochondrial and prokaryotic proton-translocating NADH:ubiquinone oxidoreductases: similarities and dissimilarities of the quinone-junction sites. J Bacteriol. 1982 Feb;149(2):612-9.

The catalytic properties of the rotenone-sensitive NADH:ubiquinone reductase (Complex I) in bovine heart submitochondrial particles and in inside-out vesicles derived from Paracoccus denitrificans and Rhodobacter capsulatus were compared.
7(0,0,1,2) Details
11080215 Talpade DJ, Greene JG, Higgins DS Jr, Greenamyre JT: In vivo labeling of mitochondrial complex I (NADH:ubiquinone oxidoreductase) in rat brain using [(3) H] dihydrorotenone. Biochem Pharmacol. 2001 Mar 1;61(5):547-54.

In vivo [(3) H] DHR binding was markedly reduced by local and systemic infusion of rotenone and was enhanced by local NADH administration.
4(0,0,0,4) Details
11325348 Cormier A, Morin C, Zini R, Tillement JP, Lagrue G: In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. 131-40.


Nicotine bound to complex I of the respiratory chain and inhibited the NADH-Ubiquinone reductase activity.
4(0,0,0,4) Details
18817789 Abdin AA, Hamouda HE: Mechanism of the neuroprotective role of coenzyme Q10 with or without L-dopa in rotenone-induced parkinsonism. IUBMB Life. 2001 Sep-Nov;52(3-5):135-41.

This model confirmed the implication of mitochondrial-apoptotic pathway in the pathogenesis of parkinsonism as there was a decrease in levels of striatal complex I activity and ATP as well as extreme overexpression of the antiapoptotic protein Bcl-2, and also exhibited the role of coenzyme Q10 where its plasma and striatal levels were found to be decreased in comparison to the normal control rats (group I).
3(0,0,0,3) Details
12914921 Grivennikova VG, Ushakova AV, Cecchini G, Vinogradov AD: Unidirectional effect of lauryl sulfate on the reversible NADH:ubiquinone oxidoreductase (Complex I). Biochem Biophys Res Commun. 1992 Nov 30;189(1):47-52.

The inhibitor affects neither NADH oxidase (coupled or uncoupled) nor NADH:ferricyanide reductase and succinate oxidase activities at the concentrations that selectively prevent the succinate-supported, rotenone-sensitive NAD (+) or ferricyanide reduction.
3(0,0,0,3) Details
8312726 Yamada K, Fukushima T: Mechanism of cytotoxicity of paraquat. J Clin Endocrinol Metab. 2008 Aug;93(8):3199-207. Epub 2008 May 20.

Paraquat also stimulated O2- production in bovine liver NADH-ubiquinone oxidoreductase (complex I).
O2- production was stimulated by paraquat even in the presence of rotenone, one of the mitochondrial respiratory chain inhibitors.
2(0,0,0,2) Details
12607133 Bernocchi P, Cargnoni A, Vescovo G, Dalla Libera L, Parrinello G, Boraso A, Ceconi C, Ferrari R: Skeletal muscle abnormalities in rats with experimentally induced heart hypertrophy and failure. Toxicol Appl Pharmacol. 2007 Jun 1;221(2):222-34. Epub 2007 Mar 23.

Activity of the different complexes of respiratory chain was investigated by means of specific inhibitors, showing major abnormalities at the level of complex I.
In fact, inhibition of VO (2) by rotenone was decreased from 83.5 +/- 3.2 to 36.4 +/- 9.6 % (p < 0.005) and from 81.8 +/- 6.1 to 38.2 +/- 7.4 % (p < 0.005) in soleus and EDL, respectively.
2(0,0,0,2) Details
10650131 Storch A, Kaftan A, Burkhardt K, Schwarz J: 1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism. Chem Biol Interact. 1997 Aug 29;106(1):15-28.


The endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline (salsolinol), which is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been reported to inhibit mitochondrial complex I (NADH-Q reductase) activity as does the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP (+)).
1(0,0,0,1) Details
11812926 Mildaziene V, Nauciene Z, Baniene R, Grigiene J: Multiple effects of 2,2',5,5'-tetrachlorobiphenyl on oxidative phosphorylation in rat liver mitochondria. J Biol Chem. 2004 Sep 17;279(38):39414-20. Epub 2004 Jul 15.

An experimental investigation of the response of the multicomponent oxidative phosphorylation system to the environmental pollutant 2,2',5,5'-tetrachlorobiphenyl (2,2',5,5'-TCB) was performed by modular kinetic analysis in rat liver mitochondria oxidizing succinate (+ rotenone) and glutamate + malate.
We explain this by the 2,2',5,5'-TCB-induced inhibition of Complex I.
1(0,0,0,1) Details
16584562 Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM: A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006 Apr 3;7:29.

DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II.
These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.
1(0,0,0,1) Details
1313376 Ahmed I, Krishnamoorthy G: The non-equivalence of binding sites of coenzyme quinone and rotenone in mitochondrial NADH-CoQ reductase. Cell Physiol Biochem. 2008;22(5-6):475-86. Epub 2008 Dec 9.

The fluorescent probe erythrosine 5'-iodoacetamide (ER) binds to mitochondrial NADH-CoQ reductase (Complex-I) accompanied by an enhancement of the fluorescence intensity.
1(0,0,0,1) Details
15265640 Alam M, Schmidt WJ: L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats. Biochem Med Metab Biol. 1994 Feb;51(1):35-42.

Peripherally and locally administered rotenone (an inhibitor of mitochondrial complex I) has been proposed as a model of Parkinson's disease (PD) as it induces nigrostriatal degeneration associated with alpha-synuclein inclusions.
1(0,0,0,1) Details
14653820 Jasso-Chavez R, Moreno-Sanchez R: Cytosol-mitochondria transfer of reducing equivalents by a lactate shuttle in heterotrophic Euglena. Biochem Soc Symp. 1999;66:85-97.

Oxalate, an inhibitor of iLDH, strongly inhibited oligomycin-sensitive respiration and growth, whereas rotenone, an inhibitor of respiratory complex I, only slightly affected these parameters in lactate-grown cells.
Oxalate, an inhibitor of iLDH, strongly inhibited oligomycin-sensitive respiration and growth, whereas rotenone, an inhibitor of respiratory complex I, only slightly affected these parameters in lactate-grown cells.
1(0,0,0,1) Details
9221826 Corsini E, Viviani B, Marinovich M, Galli CL: Role of mitochondria and calcium ions in tributyltin-induced gene regulatory pathways. Neurobiol Dis. 2006 Nov;24(2):308-17. Epub 2006 Sep 7.

Furthermore, the modulation of cellular oxidative activity induced by TBT observed with rotenone, an inhibitor of the electron entry from complex I to ubiquinone, or after prolonged treatment with ethidium bromide, an inhibitor of mitochondrial DNA and RNA synthesis, indicates mitochondria as an important intracellular source of reactive oxygen species.
Furthermore, the modulation of cellular oxidative activity induced by TBT observed with rotenone, an inhibitor of the electron entry from complex I to ubiquinone, or after prolonged treatment with ethidium bromide, an inhibitor of mitochondrial DNA and RNA synthesis, indicates mitochondria as an important intracellular source of reactive oxygen species.
1(0,0,0,1) Details
12220540 Belyaeva EA, Glazunov VV, Korotkov SM: Cyclosporin A-sensitive permeability transition pore is involved in Cd (2+)-induced dysfunction of isolated rat liver mitochondria: doubts no more. J Neural Transm. 2010 Jan;117(1):5-12. Epub 2009 Aug 26.

There is dose-dependent Cd (2+)-evoked swelling of isolated rat liver mitochondria energized by complex I, II, or IV respiratory substrates in sucrose medium in the absence of added Ca (2+) and P (i), which is prevented by Sr (2+).
Sustained activation by low [Cd (2+)] of mitochondrial basal respiration in KCl medium is observed both in the absence and in the presence of rotenone and/or oligomycin but only in the latter case (rotenone+oligomycin) CsA inhibits completely Cd (2+) activation of St 4 respiration and partially reverses DNP-uncoupled respiration depressed by cadmium.
1(0,0,0,1) Details
7622334 Armson A, Grubb WB, Mendis AH: The effect of electron transport (ET) inhibitors and thiabendazole on the fumarate reductase (FR) and succinate dehydrogenase (SDH) of Strongyloides ratti infective (L3) larvae. Neurotoxicology. 2009 Nov;30(6):977-85. Epub 2009 Sep 8.

Rotenone (a specific inhibitor of electron transport Complex I) inhibited the S. ratti FR (EC50 = 3.0 x 10 (-7) M) but not SDH.
This strongly suggests that the S. ratti FR is functionally linked with the S. ratti ET-Complex I. 2-Thenoyltrifluoroacetone (TTFA, an inhibitor of ET-Complex II) inhibited FR (EC50 = 2.6 x 10 (-5) M) and SDH (EC50 = 2.8 x 10 (-5) M) with similar effectiveness.
1(0,0,0,1) Details
17023676 Saitoh S, Zhang C, Tune JD, Potter B, Kiyooka T, Rogers PA, Knudson JD, Dick GM, Swafford A, Chilian WM: Hydrogen peroxide: a feed-forward dilator that couples myocardial metabolism to coronary blood flow. J Neurochem. 2007 Mar;100(6):1469-79. Epub 2007 Jan 4.

METHODS AND RESULTS: The production of O2*- is coupled to oxidative metabolism because inhibition of complex I (rotenone) or III (antimycin) enhanced the production of O2*- during pacing by about 50% and 400%, respectively; whereas uncoupling oxidative phosphorylation by decreasing the protonmotive force with carbonylcyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP) decreased pacing-induced O2*- production.
81(1,1,1,1) Details
17429617 Xiong K, Cai H, Luo XG, Struble RG, Clough RW, Yan XX: Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina. Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H281-8. Epub 2008 May 16.

Retinas were analyzed biochemically and anatomically 48 h following intraocular applications of mitochondrial complex I, II and IV inhibitors including rotenone, 3-nitropropionic acid and sodium azide, and plaque-containing oxidants including Fe (3+) and Abeta42 fibrils (Abeta42f).
81(1,1,1,1) Details
17477947 Hansen T, Seidel A, Borlak J: The environmental carcinogen 3-nitrobenzanthrone and its main metabolite 3-aminobenzanthrone enhance formation of reactive oxygen intermediates in human A549 lung epithelial cells. J Neurol Sci. 1999 May 1;165(1):10-7.

Mitochondrial ROS production was significantly attenuated (20% reduction) by addition of rotenone (complex I inhibition) and thenoyltrifluoroacetone (TTFA, complex II inhibition).
81(1,1,1,1) Details
11826108 Gao HM, Hong JS, Zhang W, Liu B: Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. Biochim Biophys Acta. 2006 May-Jun;1757(5-6):708-14. Epub 2006 Feb 24.

In experimental animals the exposure to a common herbicide, rotenone, induces features of parkinsonism; mechanistically, rotenone-induced destruction of dopaminergic neurons has been attributed to its inhibition of the activity of neuronal mitochondrial complex I.
81(1,1,1,1) Details
14976342 Newhouse K, Hsuan SL, Chang SH, Cai B, Wang Y, Xia Z: Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human dopaminergic SH-SY5Y cells. Biochim Biophys Acta. 2008 Nov;1777(11):1455-62. Epub 2008 Aug 22.

Though rotenone is known to be an inhibitor of the mitochondrial complex I electron transport chain, little is known about downstream pathways leading to its toxicity.
81(1,1,1,1) Details
12018892 Nakashima Y, Shinzawa-Itoh K, Watanabe K, Naoki K, Hano N, Yoshikawa S: The second coenzyme Q1 binding site of bovine heart NADH: coenzyme Q oxidoreductase. Int J Parasitol. 1995 Feb;25(2):261-3.

The rotenone-insensitive Complex I reaction in Q1 concentration range above 300 microM indicates an ordered sequential mechanism with Q1 and reduced Q1 (Q1H2) as the initial substrate to bind to the enzyme and the last product to be released from the enzyme product complex, respectively.
37(0,1,2,2) Details
16490285 Saravanan KS, Sindhu KM, Senthilkumar KS, Mohanakumar KP: L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats. Plant Physiol. 1984 Jun;75(2):414-420.

The present study investigated oxidative damage and neuroprotective effect of the antiparkinsonian drug, L-deprenyl in neuronal death produced by intranigral infusion of a potent mitochondrial complex-I inhibitor, rotenone in rats.
37(0,1,2,2) Details
14625276 Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS: Characterization of superoxide-producing sites in isolated brain mitochondria. J Physiol. 2004 May 1;556(Pt 3):755-71. Epub 2004 Feb 6.

Although rat brain mitochondria in the presence of glutamate+malate alone do generate only small amounts of H2O2 (0.04 +/- 0.02 nmol H2O2/min/mg), a substantial production is observed after the addition of the complex I inhibitor rotenone (0.68 +/- 0.25 nmol H2O2/min/mg) or in the presence of the respiratory substrate succinate alone (0.80 +/- 0.27 nmol H2O2/min/mg).
34(0,1,1,4) Details
16959493 Beretta S, Wood JP, Derham B, Sala G, Tremolizzo L, Ferrarese C, Osborne NN: Partial mitochondrial complex I inhibition induces oxidative damage and perturbs glutamate transport in primary retinal cultures. Brain Res Brain Res Protoc. 2001 Jul;7(3):267-76.

Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition.
34(0,1,1,4) Details
15953813 Naoi M, Maruyama W, Shamoto-Nagai M, Yi H, Akao Y, Tanaka M: Oxidative stress in mitochondria: decision to survival and death of neurons in neurodegenerative disorders. Proteomics. 2007 Jun;7(13):2189-200.

The interactions among these factors were studied by use of a peroxynitrite-generating agent, N-morpholino sydnonimine (SIN-1) and an inhibitor of complex I, rotenone, in human dopaminergic SH-SY5Y cells.
32(0,1,1,2) Details
7586047 Landolt JL, Ahammadsahib KI, Hollingworth RM, Barr R, Crane FL, Buerck NL, McCabe GP, McLaughlin JL: Determination of structure-activity relationships of Annonaceous acetogenins by inhibition of oxygen uptake in rat liver mitochondria. Biochemistry. 2001 Apr;66(4):435-43.

A new group of natural compounds, the Annonaceous acetogenins, have recently been determined to inhibit ATP production at a similar site of action and higher levels of potency as rotenone, i.e., at NADH-ubiquinone oxido-reductase, complex I of the mitochondrial electron-transport chain.
32(0,1,1,2) Details
18848925 Ying R, Liang HL, Whelan HT, Eells JT, Wong-Riley MT: Pretreatment with near-infrared light via light-emitting diode provides added benefit against rotenone- and MPP+-induced neurotoxicity. Am J Physiol. 1996 Nov;271(5 Pt 2):H1893-9.

The present study used these specific mitochondrial complex I inhibitors (rotenone and 1-methyl-4-phenylpyridinium or MPP (+)) on striatal and cortical neurons in culture.
32(0,1,1,2) Details
15893762 Shneyvays V, Leshem D, Shmist Y, Zinman T, Shainberg A: Effects of menadione and its derivative on cultured cardiomyocytes with mitochondrial disorders. Plant Physiol. 1988 Apr;86(4):1199-1204.

As was shown in this study, 3 microM of AK-135 restored ATP production after blockade of electron flow through mitochondrial complex I with 5 microM rotenone up to 13.18+/-1.56 vs. 3.21+/-1.12 nmol/mg protein in cells treated with rotenone only.
31(0,1,1,1) Details
1847635 Demant EJ: Inactivation of cytochrome c oxidase activity in mitochondrial membranes during redox cycling of doxorubicin. FEBS Lett. 2004 Jan 2;556(1-3):111-5.

It is related in a complex manner to the electron flux in the respiratory chain with antioxidant properties, and is maximal at the high reduction level of respiratory chain Complex I obtained in the presence of rotenone.
31(0,1,1,1) Details
2871147 Sugiyama Y, Fujita T, Matsumoto M, Okamoto K, Imada I: Effects of idebenone (CV-2619) and its metabolites on respiratory activity and lipid peroxidation in brain mitochondria from rats and dogs. J Neurosci Res. 2000 May 15;60(4):552-8.

These facts and results of inhibitor analysis suggest that the action site of CV-2619 is NADH-linked complex I in the mitochondrial respiratory chain and is different from that of inhibitors of oxidative phosphorylation such as rotenone, oligomycin and 2,4-dinitrophenol.
31(0,1,1,1) Details
10762084 Chinopoulos C, Tretter L, Adam-Vizi V: Reversible depolarization of in situ mitochondria by oxidative stress parallels a decrease in NAD (P) H level in nerve terminals. J Pharmacobiodyn. 1985 Dec;8(12):1006-17.

The effect of H2O2 on delta (psi) m in the presence of the complex I inhibitor, rotenone, was also unaltered by addition of catalase.
31(0,1,1,1) Details
18804145 Kaneko K, Hineno A, Yoshida K, Ikeda S: Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice. J Biochem. 1983 Oct;94(4):1301-6.

Rotenone, a selective mitochondrial complex I inhibitor, induces neurodegeneration mimicking Parkinson's disease.
31(0,1,1,1) Details
15729575 Artwohl M, Furnsinn C, Waldhausl W, Holzenbein T, Rainer G, Freudenthaler A, Roden M, Baumgartner-Parzer SM: Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPARgamma-independent mechanism. Curr Alzheimer Res. 2009 Sep 28.

Proliferation inhibition and lactate release were mimicked by rotenone (mitochondrial complex I inhibitor).
31(0,1,1,1) Details
19445904 Huang J, Hao L, Xiong N, Cao X, Liang Z, Sun S, Wang T: Involvement of glyceraldehyde-3-phosphate dehydrogenase in rotenone-induced cell apoptosis: relevance to protein misfolding and aggregation. J Neurochem. 2004 Jul;90(2):405-21.

We found that rotenone, a common mitochondrial complex I inhibitor used to produce experimental parkinsonism, cannot only induce GAPDH translocation but also trigger intermolecular disulfide bonding and result in the formation of intracytoplasmic aggregates of GAPDH.
31(0,1,1,1) Details
12919951 Liu Y, Zhao H, Li H, Kalyanaraman B, Nicolosi AC, Gutterman DD: Mitochondrial sources of H2O2 generation play a key role in flow-mediated dilation in human coronary resistance arteries. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1447-58.

Diameter changes to increases in pressure gradients (20 and 100 cm H2O) were examined in the absence and the presence of rotenone (1 micromol/L), myxothiazol (100 nmol/L), cyanide (1 micromol/L), mitochondrial complex I, III, and IV inhibitors, respectively, and apocynin (3 mmol/L), a NADPH oxidase inhibitor.
31(0,1,1,1) Details
9614211 De Kimpe SJ, Anggard EE, Carrier MJ: Reactive oxygen species regulate macrophage scavenger receptor type I, but not type II, in the human monocytic cell line THP-1. PLoS One. 2010 Mar 10;5(3):e9532.

Several sources of reactive oxygen species are involved as inhibition of MSR activity and levels of MSR-I mRNA occurred in the presence of rotenone, a mitochondrial complex I inhibitor, or acetovanillone, a NADPH oxidase inhibitor.
31(0,1,1,1) Details
16686429 Lopez-Barneo J, Ortega-Saenz P, Piruat JI, Garcia-Fernandez M: Oxygen-sensing by ion channels and mitochondrial function in carotid body glomus cells. J Neurochem. 2005 Nov;95(4):930-9. Epub 2005 Aug 10.

However, rotenone, a complex I blocker, selectively occludes the responsiveness to hypoxia of glomus cells in a dose-dependent manner.
6(0,0,1,1) Details
19220002 King MS, Sharpley MS, Hirst J: Reduction of hydrophilic ubiquinones by the flavin in mitochondrial NADH:ubiquinone oxidoreductase (Complex I) and production of reactive oxygen species. J Neurosci Res. 2003 Nov 15;74(4):589-97.

Hydrophilic ubiquinones are reduced by an additional, non-energy-transducing pathway (which is insensitive to inhibitors such as rotenone and piericidin A).
6(0,0,0,6) Details
12351220 Helmerhorst EJ, Murphy MP, Troxler RF, Oppenheim FG: Characterization of the mitochondrial respiratory pathways in Candida albicans. Eur J Biochem. 1996 Nov 1;241(3):888-94.

In addition, malate/pyruvate respiration was rotenone-sensitive, and an enzyme activity assay further confirmed that C. albicans cells express Complex I activity.
6(0,0,1,1) Details
3134026 Tanaka M, Nishikimi M, Suzuki H, Ozawa T, Ichiki T, Kobayashi M, Wada Y: Variation in the levels of complex I subunits among tissues in a patient with mitochondrial encephalomyopathy and renal dysfunction. Am J Physiol Lung Cell Mol Physiol. 2002 Nov;283(5):L922-31.

Rotenone-sensitive NADH-cytochrome c reductase activity was decreased in all the tissues examined, but the degree of deficiency varied from tissue to tissue.
4(0,0,0,4) Details
20074573 Nakamaru-Ogiso E, Han H, Matsuno-Yagi A, Keinan E, Sinha SC, Yagi T, Ohnishi T: The ND2 subunit is labeled by a photoaffinity analogue of asimicin, a potent complex I inhibitor. Neurochem Res. 2009 Aug;34(8):1469-78. Epub 2009 Feb 28.

The cross-linking was blocked by rotenone.
4(0,0,0,4) Details
8443212 Sled VD, Vinogradov AD: Kinetics of the mitochondrial NADH-ubiquinone oxidoreductase interaction with hexammineruthenium (III). Trends Neurosci. 2001 May;24(5):245-7.

Qualitatively the same results were obtained using submitochondrial particles or isolated Complex I.
Both hexammineruthenium (III) and ferricyanide reduction was rotenone-insensitive and showed no stimulation by the uncouplers in tightly coupled submitochondrial particles.
3(0,0,0,3) Details
7957254 Finel M, Majander AS, Tyynela J, De Jong AM, Albracht SP, Wikstrom M: Isolation and characterisation of subcomplexes of the mitochondrial NADH:ubiquinone oxidoreductase (complex I). Nat Neurosci. 2000 Dec;3(12):1301-6.

In addition, the Q-1 reductase activity of all the subcomplexes is insensitive to rotenone.
3(0,0,0,3) Details
3106581 Nishizawa M, Tanaka K, Shinozawa K, Kuwabara T, Atsumi T, Miyatake T, Ohama E: A mitochondrial encephalomyopathy with cardiomyopathy. Neurology. 2002 Feb 26;58(4 Suppl 1):S9-18.

A case revealing a defect of complex I in the respiratory chain..
The rotenone-sensitive NADH-coenzyme Q reductase activity was markedly decreased in heart, skeletal muscle and liver mitochondria.
3(0,0,0,3) Details
14972026 Johansson FI, Michalecka AM, Moller IM, Rasmusson AG: Oxidation and reduction of pyridine nucleotides in alamethicin-permeabilized plant mitochondria. Drugs Exp Clin Res. 1999;25(2-3):87-97.

AlaM was found to inhibit the electron-transport chain at the external Ca2+-dependent rotenone-insensitive NADH dehydrogenase and around complexes III and IV.
Nevertheless, under optimal conditions, especially complex I-mediated NADH oxidation in AlaM-treated mitochondria was much higher than what has been previously measured by other techniques.
2(0,0,0,2) Details
16917840 Imamura K, Takeshima T, Kashiwaya Y, Nakaso K, Nakashima K: D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease. J Neurochem. 1996 Apr;66(4):1617-24.

Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro.
2(0,0,0,2) Details
1645458 Bienen EJ, Saric M, Pollakis G, Grady RW, Clarkson AB Jr: Mitochondrial development in Trypanosoma brucei brucei transitional bloodstream forms. Toxicol Sci. 2002 Feb;65(2):220-7.

The EMF is inhibited by 2,4-dinitrophenol, rotenone and salicylhydroxamic acid but not by antimycin A or cyanide.
This putative production is either by F1F0 ATPase driven by the complex I proton pump or by mitochondrial substrate level phosphorylation, or most likely by both.
1(0,0,0,1) Details
11696188 Svensson AS, Rasmusson AG: Light-dependent gene expression for proteins in the respiratory chain of potato leaves. Biochem J. 2007 Aug 15;406(1):125-9.

The recently characterized nda1 and ndb1 genes, homologues to genes encoding the non-proton pumping respiratory chain NADH-dehydrogenases of Escherichia coli and yeast, were compared to genes encoding catalytic subunits of the proton-pumping NADH dehydrogenase (complex I).
As leaves develop from young to mature, the nda1 transcript level increases, accompanied by an elevation in immunodetected NDA protein and internal rotenone-insensitive NADH oxidation.
1(0,0,0,1) Details
18802751 Xiong Y, Ding H, Xu M, Gao J: Protective effects of asiatic acid on rotenone- or H2O2-induced injury in SH-SY5Y cells. FEBS Lett. 1992 Apr 6;300(3):275-8.

Mitochondrial dysfunction occurred in PD patients showing a 15-30% loss of activity in complex I.
1(0,0,0,1) Details
9070626 Sriram K, Pai KS, Boyd MR, Ravindranath V: Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice. J Neurochem. 2002 Dec;83(5):1094-102.

In the striatum significant inhibition of rotenone-sensitive NADH ubiquinone-1 oxido-reductase (Complex 1) was observed transiently 1 h after MPTP administration.
The enzyme activity recovered thereafter; significant inhibition of mitochondrial Complex I was observed in the striatum only 18 h after MPTP dose.
1(0,0,0,1) Details
11064159 Lopez-Torres M, Romero M, Barja G: Effect of thyroid hormones on mitochondrial oxygen free radical production and DNA oxidative damage in the rat heart. Antioxid Redox Signal. 2005 May-Jun;7(5-6):630-8.


Studies with respiratory inhibitors showed that the decrease in oxygen radical generation observed in hypothyroidism occurred at Complex III (mainly) and at Complex I; that decrease was due to the presence of a lower free radical leak in the respiratory chain (P <0.05).
1(0,0,0,1) Details
17027047 Watabe M, Nakaki T: ATP depletion does not account for apoptosis induced by inhibition of mitochondrial electron transport chain in human dopaminergic cells. Ann Neurol. 2008 Nov;64(5):555-65.

To date, ETC complex (I-IV) inhibitors (ETCIs) have been thought to induce ATP depletion, triggering cellular apoptosis.
In human dopaminergic SH-SY5Y cells, ETCIs (rotenone, thenoyltrifluoroacetone, antimycin A and potassium cyanide) depleted ATP and induced apoptosis.
1(0,0,0,1) Details
16344601 French SW: The pathogenesis and significance of the urinary alcohol cycle in rats fed ethanol intragastrically. Alcohol Clin Exp Res. 2005 Nov;29(11 Suppl):158S-161S.

When complex I (NADH dehydrogenase) of the mitochondrial electron transport chain is inhibited by feeding rotenone, the cycle is totally eliminated and blood alcohol levels remain constant at 200 mg/%.
81(1,1,1,1) Details
20089711 Zoer B, Cogolludo AL, Perez-Vizcaino F, De Mey JG, Blanco CE, Villamor E: Hypoxia sensing in the fetal chicken femoral artery is mediated by the mitochondrial electron transport chain. Brain Res. 2000 Feb 7;855(1):67-75.

Hypoxia-induced relaxation was abolished or significantly reduced by the mETC inhibitors rotenone (complex I), myxothiazol and antimycin A (complex III), and NaN (3) (complex IV).
81(1,1,1,1) Details
12601064 Yang JH, Basinger SF, Gross RL, Wu SM: Blue light-induced generation of reactive oxygen species in photoreceptor ellipsoids requires mitochondrial electron transport. J Inherit Metab Dis. 1996;19(5):675-86.

Rotenone or antimycin A, the respiratory electron transport blockers at complex I and III, respectively, significantly suppressed the light-evoked generation of rOx.
81(1,1,1,1) Details
19616571 Alam M, Danysz W, Schmidt WJ, Dekundy A: Effects of glutamate and alpha2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats. Biochim Biophys Acta. 2004 Oct 4;1658(3):244-51.

Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD).
81(1,1,1,1) Details
19580850 Tantucci M, Mariucci G, Taha E, Spaccatini C, Tozzi A, Luchetti E, Calabresi P, Ambrosini MV: Induction of heat shock protein 70 reduces the alteration of striatal electrical activity caused by mitochondrial impairment. Biochem J. 1994 Jul 1;301 ( Pt 1):161-7.

Corticostriatal slices from rats that had undergone mild thermal stress were exposed to either rotenone or 3-nitropropionic acid (3-NP), that selectively inhibits mitochondrial complex I and complex II, respectively.
81(1,1,1,1) Details
18508033 Chen YY, Chen G, Fan Z, Luo J, Ke ZJ: GSK3beta and endoplasmic reticulum stress mediate rotenone-induced death of SK-N-MC neuroblastoma cells. J Bioenerg Biomembr. 2005 Feb;37(1):1-15.

Rotenone, an environmental toxin that inhibits mitochondrial complex I, has been used to induce experimental Parkinsonism in animals and cell cultures.
81(1,1,1,1) Details
10477266 Ferreirinha F, Duarte M, Melo AM, Videira A: Effects of disrupting the 21 kDa subunit of complex I from Neurospora crassa. Biochem J. 1999 Sep 15;342 Pt 3:551-4.

Nevertheless, complex I of nuo21 is able to perform NADH:ubiquinone reductase activity, as judged by the observation that the respiration of mutant mitochondria is sensitive to inhibition by rotenone.
36(0,1,1,6) Details
7823960 Hofhaus G, Attardi G: Efficient selection and characterization of mutants of a human cell line which are defective in mitochondrial DNA-encoded subunits of respiratory NADH dehydrogenase. Biokhimiia. 1994 Nov;59(11):1638-45.

In the course of analysis of eight mutants of the human cell line VA2B selected for their resistance to high concentrations of the complex I inhibitor rotenone, seven were found to be respiration deficient, and among these, six exhibited a specific defect of complex I.
36(0,1,1,6) Details
16777535 van der Merwe JA, Dubery IA: Benzothiadiazole inhibits mitochondrial NADH:ubiquinone oxidoreductase in tobacco. Neuropharmacology. 2007 Feb;52(2):536-41. Epub 2006 Oct 5.

Using a dichlorodihydrofluorescein assay, it was found that benzothiadiazole, salicylic acid and the complex I inhibitor rotenone, increased reactive oxygen species production within cells in a concentration-dependent manner.
34(0,1,1,4) Details
9309707 Lenaz G, Bovina C, Castelluccio C, Fato R, Formiggini G, Genova ML, Marchetti M, Pich MM, Pallotti F, Parenti Castelli G, Biagini G: Mitochondrial complex I defects in aging. J Immunol. 2004 Dec 1;173(11):6973-80.

In a study of Complex I activity in human platelet membranes we found that the enzyme activity was unchanged but the titre for half-inhibition by rotenone was significantly increased in aged individuals and proposed this change as a suitable biomarker of aging and age-related diseases.
34(0,1,1,4) Details
15581661 Alam M, Schmidt WJ: Mitochondrial complex I inhibition depletes plasma testosterone in the rotenone model of Parkinson's disease. J Biol Chem. 2008 Aug 22;283(34):23179-88. Epub 2008 Jun 18.

In rats, rotenone, a mitochondrial complex I inhibitor, causes specific nigral dopaminergic neurodegeneration producing parkinsonian symptoms.
32(0,1,1,2) Details
16965838 Tretter L, Mayer-Takacs D, Adam-Vizi V: The effect of bovine serum albumin on the membrane potential and reactive oxygen species generation in succinate-supported isolated brain mitochondria. Eur J Biochem. 1992 Sep 1;208(2):481-5.

The high rate of H (2) O (2) generation measured in mitochondria prepared with digitonin (600.6+/-26.8pmol/min/mg protein) was inhibited by rotenone, consistently with a reverse flow of electrons via complex I.
31(0,1,1,1) Details
15764812 Singh SV, Srivastava SK, Choi S, Lew KL, Antosiewicz J, Xiao D, Zeng Y, Watkins SC, Johnson CS, Trump DL, Lee YJ, Xiao H, Herman-Antosiewicz A: Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Appl Physiol. 1998 Feb;84(2):479-85.

The SFN-induced ROS generation was significantly attenuated on pretreatment with mitochondrial respiratory chain complex I inhibitors, including diphenyleneiodonium chloride and rotenone.
31(0,1,1,1) Details
19482916 Giraud E, Van Aken O, Ho LH, Whelan J: The transcription factor ABI4 is a regulator of mitochondrial retrograde expression of ALTERNATIVE OXIDASE1a. Neurosci Lett. 2008 Nov 28;446(1):56-8. Epub 2008 Sep 11.

This approach identified a strong repressor element, designated the B element, that was necessary for an increased promoter activity in response to the mitochondrial complex I inhibitor rotenone.
31(0,1,1,1) Details
17442543 Tan QR, Wang XZ, Wang CY, Liu XJ, Chen YC, Wang HH, Zhang RG, Zhen XC, Tong Y, Zhang ZJ: Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells. Sheng Li Xue Bao. 2007 Jun 25;59(3):253-9.

In the present study, we compared the atypical agents, risperidone (RIP), olanzapine (OLZ), and quetiapine (QTP), with the classical agent haloperidol (HAL) in reducing cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor, in PC12 cells.
31(0,1,1,1) Details
15026259 Bashkatova V, Alam M, Vanin A, Schmidt WJ: Chronic administration of rotenone increases levels of nitric oxide and lipid peroxidation products in rat brain. Eur Neuropsychopharmacol. 2007 Dec;17(12):768-73. Epub 2007 Apr 17.

The complex I inhibitor rotenone is a neurotoxin that has been proposed to induce Parkinson-like degeneration.
31(0,1,1,1) Details
10762085 Seyfried J, Soldner F, Kunz WS, Schulz JB, Klockgether T, Kovar KA, Wullner U: Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells. Biochim Biophys Acta. 2008 May;1777(5):397-403. Epub 2008 Mar 18.

Similarly, the complex I-inhibitor rotenone induced a time-dependent loss of GSH at 1 and 10 microM, whereas treatment with lower concentrations of rotenone (0.1, 0.01 microM) increased cellular GSH.
31(0,1,1,1) Details
10378416 Chen M, Andersen LP, Zhai L, Kharazmi A: Characterization of the respiratory chain of Helicobacter pylori. Biochim Biophys Acta. 1997 Apr 11;1319(2-3):223-32.

The total insensitivity of activities of NADH dehydrogenase to rotenone and of NADH-cytochrome c reductase to antimycin is indicative of the absence of the classical complex I of the electron transfer chain in this bacterium.
31(0,1,1,1) Details
18053146 Telang S, Lane AN, Nelson KK, Arumugam S, Chesney J: The oncoprotein H-RasV12 increases mitochondrial metabolism. . Pest Manag Sci. 2001 Oct;57(10):932-40.

Importantly, ectopic expression of H-RasV12 sensitized immortalized cells to the ATP-depleting and cytotoxic effects of electron transport perturbation using the complex I inhibitor rotenone.
31(0,1,1,1) Details
15806174 Lee YJ, Lee DH, Cho CK, Chung HY, Bae S, Jhon GJ, Soh JW, Jeoung DI, Lee SJ, Lee YS: HSP25 inhibits radiation-induced apoptosis through reduction of PKCdelta-mediated ROS production. Arch Microbiol. 2008 Oct;190(4):471-80. Epub 2008 Jun 13.

In the present study, radiation-induced cytochrome c release from mitochondria and activation of caspases accompanied by a decrease of mitochondrial membrane potential in Jurkat T cells were shown to be inhibited by mitochondrial complex I inhibitor rotenone, suggesting that mitochondrial ROS might be important in radiation-induced caspase-dependent apoptosis.
31(0,1,1,1) Details
15909418 Tkachenko HM, Kurhaliuk NM, Vovkanych LS: [Effect of K-ATP channel opener-pinacidil on the liver mitochondria function in rats with different resistance to hypoxia during stress]. J Biol Chem. 1994 Jan 21;269(3):2263-9.

The additional analyses were conducted with the use of inhibitors: mitochondrial enzyme complex I 10 mM rotenone and succinate dehydrohenase 2 mM malonic acid.
31(0,1,1,1) Details
18567707 Gao Q, Wolin MS: Effects of hypoxia on relationships between cytosolic and mitochondrial NAD (P) H redox and superoxide generation in coronary arterial smooth muscle. FASEB J. 2006 Feb;20(2):259-68.

Rotenone appeared to increase mitochondrial NAD (P) H and superoxide, suggesting hypoxia could increase superoxide generation by complex I.
6(0,0,1,1) Details
8986635 Pitkanen S, Raha S, Robinson BH: Diagnosis of complex I deficiency in patients with lactic acidemia using skin fibroblast cultures. J Biol Chem. 1999 Jan 29;274(5):2625-30.

Values for NADH-cytochrome c reductase (rotenone sensitive) were compared for a series of three controls and nine patients with complex I (NADH-coenzyme Q reductase deficiency).
6(0,0,1,1) Details
16725203 Kou J, Klorig DC, Bloomquist JR: Potentiating effect of the ATP-sensitive potassium channel blocker glibenclamide on complex I inhibitor neurotoxicity in vitro and in vivo. Biochem J. 2006 Apr 15;395(2):405-15.

We measured the ability of mitochondrial inhibitors of complexes I (rotenone, MPP (+), and HPP (+)), II (amdro), IV (Na cyanide), and an uncoupler (dinoseb) to release preloaded dopamine from murine striatal synaptosomes.
4(0,0,0,4) Details
9119899 Kilbourn MR, Charalambous A, Frey KA, Sherman P, Higgins DS Jr, Greenamyre JT: Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I. Ann Neurol. 1988 Mar;23(3):287-94.

4(0,0,0,4) Details
18140 Ragan CI, Bloxham DP: Specific labelling of a constituent polypeptide of bovine heart mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone reductase by the inhibitor diphenyleneiodonium. J Neurol Sci. 1987 Apr;78(2):189-201.

Rotenone increased the apparent affinity of diphenyleneiodonium for the 23500-mol.wt. polypeptide without affecting the maximum incorporation. 8.
NADH-ubiquinone-1 and NADH-menadione reductase activities of Complex I were inhibited by diphenyleneiodonium (apparent Ki 23 and 30 nmol/mg of protein respectively).
3(0,0,0,3) Details
9707444 Bai Y, Attardi G: The mtDNA-encoded ND6 subunit of mitochondrial NADH dehydrogenase is essential for the assembly of the membrane arm and the respiratory function of the enzyme. Neurochem Res. 2009 Jun 4.


Seven of the approximately 40 subunits of the mammalian respiratory NADH dehydrogenase (Complex I) are encoded in mitochondrial DNA (mtDNA).
2(0,0,0,2) Details
7797367 Fukushima T, Isobe A, Joho N, Shiwaku K, Yamane Y, Torii M: The fatty acids of each lipid fraction and their use in providing energy source of the plerocercoid of Spirometra erinacei. Int J Parasitol. 1991 Dec;21(8):965-8.

Michaelis constants (Km) of beta-hydroxyacyl-CoA dehydrogenase (HAD), NADH: ubiquinone oxidoreductase (complex I) (NADH: ferricyanide reaction) and complex I (NADH: ubiquinone reaction) for NADH were 20.6, 50 and 13.3 microM, respectively.
The ATP production in mitochondria of the plerocercoids was accelerated by adding ADP and inhibited by adding such electron transport system inhibitors as rotenone, antimycin A and sodium cyanide.
2(0,0,0,2) Details
9831004 Pezzi PP, De Negri AM, Sadun F, Carelli V, Leuzzi V: Childhood Leber's hereditary optic neuropathy (ND1/3460) with visual recovery. J Neurosci Res. 2007 Nov 15;85(15):3471-9.

The specific activity of complex I in platelets was reduced in the proband and normal in his relatives.
An abnormal resistance of NADH:ubiquinone reductase to the inhibitory effect of rotenone was found in platelet mitochondria from the proband and family members and was consistent with the degree of heteroplasmy.
2(0,0,0,2) Details
9155526 Cornelissen J, Van Kuilenburg AB, Voute PA, Van Gennip AH: The effect of the neuroblastoma-seeking agent meta-iodobenzylguanidine (MIBG) on NADH-driven superoxide formation and NADH-driven lipid peroxidation in beef heart submitochondrial particles. Cytometry A. 2010 Apr;77(4):310-20.

MIBG is a structural analogue of noradrenaline and is capable of inhibiting complex I and complex III of the respiratory chain.
The effect of MIBG is comparable to that of rotenone (an inhibitor of complex I) rather than that of antimycin (an inhibitor of complex III).
2(0,0,0,2) Details
16292513 Lee SJ, Youn YC, Han ES, Lee CS: Depressant effect of mitochondrial respiratory complex inhibitors on proteasome inhibitor-induced mitochondrial dysfunction and cell death in PC12 cells. J Biol Chem. 2005 Dec 30;280(52):42655-68. Epub 2005 Oct 19.

The addition of rotenone (inhibitor of respiratory complex I), 3-nitropropionic acid (complex II inhibitor), harmine (inhibitor of complexes I and II) and cyclosporin A (CsA, an inhibitor of the mitochondrial permeability transition) reduced the nuclear damage, loss in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with MG132, a proteasome inhibitor.
The addition of rotenone (inhibitor of respiratory complex I), 3-nitropropionic acid (complex II inhibitor), harmine (inhibitor of complexes I and II) and cyclosporin A (CsA, an inhibitor of the mitochondrial permeability transition) reduced the nuclear damage, loss in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with MG132, a proteasome inhibitor.
2(0,0,0,2) Details
19577342 Caro P, Gomez J, Sanchez I, Lopez-Torres M, Barja G: [Effect of restricting amino acids except methionine on mitochondrial oxidative stress]. J Pharmacol Exp Ther. 2004 Dec;311(3):948-53. Epub 2004 Jul 27.


ROS production in isolated liver mitochondria was unchanged with complex I (pyruvate/malate or glutamate/malate) or complex II (succinate) linked substrates.
1(0,0,0,1) Details
15451049 Bretaud S, Lee S, Guo S: Sensitivity of zebrafish to environmental toxins implicated in Parkinson's disease. Comp Biochem Physiol A Mol Integr Physiol. 2002 May;132(1):107-9.

One valuable type of animal model for PD is established by treating animals with PD-inducing neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat.
These neurotoxins are thought to inhibit mitochondrial complex I activity leading to oxidative stress, impaired energy metabolism, proteasomal dysfunction, and, eventually, dopamine neuronal loss.
1(0,0,0,1) Details
39543 Takeshige K, Minakami S: NADH- and NADPH-dependent formation of superoxide anions by bovine heart submitochondrial particles and NADH-ubiquinone reductase preparation. J Neurochem. 2000 Dec;75(6):2611-21.

The effects of pH and inorganic salts at high concentrations on the NADH- and NADPH-dependent reactions of Complex I were essentially similar to those on the reactions of submitochondrial particles. 3.
The reaction was inhibited by treatment of the preparation with p-hydroxymercuribenzoate and stimulated by treatment with rotenone.
1(0,0,0,1) Details
494059 Breen GA, Scheffler IE: Respiration-deficient Chinese hamster cell mutants: biochemical characterization. Somatic Cell Genet. 1979 Jul;5(4):441-51.

We show that these mutants all have a defect in complex I of the electron-transport chain.
The general features of these mutants are: (1) a low rate of O2 consumption in whole cells; (2) a low rate of release of 14CO2 from [2-14C] pyruvate, [1-14C] pyruvate, and [3-14C] beta-hydroxybutyrate; (3) a low rate of release of 14CO2 from [5-14C] glutamate and [1-14C] glutamate in mutants from groups II, VII, and the "overlapping" mutant, whereas a significant amount of 14CO2 is released in mutants from group I; (4) a substantial rate of release of 14CO2 from [U-14C] asparate; (5) in isolated mitochondria, succinate and alpha-glycerol phosphate stimulate O2 consumption whereas substrates which generate NADH, such as malate, do not; and (6) there is little or no rotenone-sensitive NADH oxidase activity in isolated mitochondria.
1(0,0,0,1) Details
10917650 Lummen P: Biochemical aspects of N-heterocyclic complex-I inhibitors with insecticidal activity. Biochem Soc Trans. 1999 Aug;27(4):602-6.

1(0,0,0,1) Details
7476924 van de Water B, Zoeteweij JP, de Bont HJ, Nagelkerke JF: Inhibition of succinate:ubiquinone reductase and decrease of ubiquinol in nephrotoxic cysteine S-conjugate-induced oxidative cell injury. Brain Res. 2004 Jul 23;1015(1-2):73-81.

KCN cytoprotection could be prevented by inhibition of SQR activity with oxaloacetate or TTFA, whereas inhibition of either complex I or III with rotenone and antimycin, respectively, did not prevent it.
The DCVC-induced oxidative stress was associated with a decrease in the succinate:ubiquinone reductase (SQR) activity of complex II, whereas NADH:ubiquinone reductase activity of complex I remained unaffected.
1(0,0,0,1) Details
15280438 Watabe M, Nakaki T: Rotenone induces apoptosis via activation of bad in human dopaminergic SH-SY5Y cells. J Neurosci. 2007 Jul 4;27(27):7310-7.

Chronic complex I inhibition caused by rotenone induces features of Parkinson's disease in rats, including selective nigrostriatal dopaminergic degeneration and Lewy bodies with alpha-synuclein-positive inclusions.
81(1,1,1,1) Details
8638946 Tein I, Bukovac SW, Xie ZW: Characterization of the human plasmalemmal carnitine transporter in cultured skin fibroblasts. J Neurosci Res. 2002 Aug 15;69(4):559-66.

The effects of different site-specific respiratory chain toxins, namely, rotenone (complex I), antimycin A (complex III), and potassium cyanide (KCN) (complex IV) on carnitine uptake was also examined.
81(1,1,1,1) Details
15215104 Mills SD, Yang W, MacCormack K: Molecular characterization of benzimidazole resistance in Helicobacter pylori. Antimicrob Agents Chemother. 2004 Jul;48(7):2524-30.

MIC testing of the wild-type H. pylori strain and four classes of nuo mutants revealed that all NuoD mutant classes were hypersensitive to rotenone, a known inhibitor of complex I (NADH:ubiquinone oxidoreductase) suggested to bind to NuoD.
81(1,1,1,1) Details
16115719 Hirata Y, Nagatsu T: Rotenone and CCCP inhibit tyrosine hydroxylation in rat striatal tissue slices. Biochem Pharmacol. 2008 Jul 1;76(1):128-38. Epub 2008 Apr 29.

Complex I inhibition has been implicated in the neurotoxicity of MPTP and rotenone, which reproduce a neurochemical and neuropathological feature of Parkinson's disease in experimental animals.
81(1,1,1,1) Details
9199966 Katsikis PD, Garcia-Ojeda ME, Torres-Roca JF, Greenwald DR, Herzenberg LA, Herzenberg LA: HIV type 1 Tat protein enhances activation-but not Fas (CD95)-induced peripheral blood T cell apoptosis in healthy individuals. Toxicon. 2003 Sep 15;42(4):351-7.

Examining the mechanisms by which Tat induces apoptosis, we found that inhibitors of reactive oxygen intermediate (ROI) generation or neutralizers of ROI, such as rotenone, a potent inhibitor of mitochondrial complex I of the respiratory chain, and 3,3,5,5-tetramethylpyrroline N-oxide (TMPO), an electron spin trap, could both enhance the spontaneous apoptosis induced by Tat.
81(1,1,1,1) Details
19088429 Oliver R 3rd, Friday E, Turturro F, Welbourne T: Troglitazone induced cytosolic acidification via extracellular signal-response kinase activation and mitochondrial depolarization: complex I proton pumping regulates ammoniagenesis in proximal tubule-like LLC-PK1 cells. Biol Pharm Bull. 1999 Mar;22(3):240-3.

TRO-enhanced acid production was correlated with mitochondrial membrane potential and rotenone and 5-(N-ethyl-N-isopropyl) amiloride, were employed to test specifically the role of Complex I proton pumping.
36(0,1,1,6) Details
17038483 Richardson JR, Caudle WM, Guillot TS, Watson JL, Nakamaru-Ogiso E, Seo BB, Sherer TB, Greenamyre JT, Yagi T, Matsuno-Yagi A, Miller GW: Obligatory role for complex I inhibition in the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9893-8.

Recently, we reported that the yeast single-subunit nicotinamide adenine dinucleotide (reduced) dehydrogenase (NDI1) is resistant to rotenone, a complex I inhibitor that produces a parkinsonian syndrome in rats, and that overexpression of NDI1 in SK-N-MC cells prevents the toxicity of rotenone.
36(0,1,1,6) Details
12180906 Kushnareva Y, Murphy AN, Andreyev A: Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD (P)+ oxidation-reduction state. Exp Cell Res. 1999 Jun 15;249(2):396-403.

This increased ROS production can be mimicked by rotenone, a complex I inhibitor, as well as other chemical inhibitors of electron flow that act further downstream in the electron transport chain.
34(0,1,1,4) Details
12911637 Hoglinger GU, Carrard G, Michel PP, Medja F, Lombes A, Ruberg M, Friguet B, Hirsch EC: Dysfunction of mitochondrial complex I and the proteasome: interactions between two biochemical deficits in a cellular model of Parkinson's disease. J Physiol. 2002 Nov 1;544(Pt 3):687-93.

Proteasome inhibition potentiated the toxicity of rotenone, MPP+ and 6-hydroxydopamine at concentrations at which they increased free radical levels >/= 40% above baseline, exceeding the cellular capacity to detoxify oxidized proteins reduced by proteasome inhibition, and also exacerbated ATP depletion caused by complex I inhibition.
34(0,1,1,4) Details
1900156 Anderson WM, Chambers BB, Wood JM, Benninger L: Inhibitory effects of two structurally related carbocyanine laser dyes on the activity of bovine heart mitochondrial and Paracoccus denitrificans NADH-ubiquinone reductase. Novartis Found Symp. 2006;272:54-64; discussion 64-72

The mechanism of inhibition (except for the HIDC effect on coenzyme Q1 reduction with P. denitrificans) appeared to be through the interaction of dye with the rotenone site on NADH-ubiquinone reductase (EC 1.6.99.3), since rotenone-insensitive preparations of complex I and P. denitrificans membrane vesicles were also insensitive to HIDC and HITC inhibition.
33(0,1,1,3) Details
7931358 Hartley A, Stone JM, Heron C, Cooper JM, Schapira AH: Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson's disease. J Biol Chem. 2010 Jan 15;285(3):2040-50. Epub 2009 Nov 4.

We have investigated the mode of death induced by complex I inhibition of dopaminergic cell cultures, and our results suggest that both 1-methyl-4-phenylpyridinium and rotenone cause apoptosis at low concentrations and necrosis at high concentrations.
32(0,1,1,2) Details
11078378 Yuki K, Miyauchi T, Kakinuma Y, Murakoshi N, Suzuki T, Hayashi J, Goto K, Yamaguchi I: Mitochondrial dysfunction increases expression of endothelin-1 and induces apoptosis through caspase-3 activation in rat cardiomyocytes in vitro. J Neurochem. 2002 Jul;82(1):66-74.

Therefore, in order to elucidate this problem, we developed an in vitro model of mitochondrial dysfunction using rotenone, a mitochondrial respiratory chain complex I inhibitor, and studied preproendothelin-1 gene expression and apoptosis.
31(0,1,1,1) Details
17176833 Bondarenko OI, Sahach VF: [Role of mitochondria in reglulation of endothelial cell hyperpolarization to acetylcholine]. Fiziol Zh. 2006;52(5):6-11.

Protonofore CCCP and rotenone, an electron transport chain complex I inhibitor, agents that cause mitochondria depolarization, inhibited the sustained hyperpolarization of endothelial cells.
31(0,1,1,1) Details
16686432 Nurse CA, Buttigieg J, Thompson R, Zhang M, Cutz E: Oxygen sensing in neuroepithelial and adrenal chromaffin cells. Novartis Found Symp. 2006;272:106-14; discussion 114-8

For example, the complex I blocker, rotenone (1 microM), mimics hypoxia in causing K+ channel inhibition and ATP secretion, and occludes hypoxic sensitivity.
31(0,1,1,1) Details
10514095 Duan W, Zhang Z, Gash DM, Mattson MP: Participation of prostate apoptosis response-4 in degeneration of dopaminergic neurons in models of Parkinson's disease. Exp Lung Res. 2002 Jul-Aug;28(5):373-89.

Exposure of cultured human dopaminergic neural cells to the complex I inhibitor rotenone, or to Fe2+, resulted in Par-4 induction, mitochondrial dysfunction, and subsequent apoptosis.
31(0,1,1,1) Details
18486118 Rojas JC, Saavedra JA, Gonzalez-Lima F: Neuroprotective effects of memantine in a mouse model of retinal degeneration induced by rotenone. Biochem J. 2002 Dec 1;368(Pt 2):545-53.

We tested the hypothesis that uncompetitive NMDAR blockade with memantine prevents mitochondrial dysfunction-related neurodegeneration in vivo, using a mouse model of retinal ganglion cell layer (GCL) degeneration induced by rotenone, a mitochondrial complex I inhibitor.
31(0,1,1,1) Details
10908611 Luetjens CM, Bui NT, Sengpiel B, Munstermann G, Poppe M, Krohn AJ, Bauerbach E, Krieglstein J, Prehn JH: Delayed mitochondrial dysfunction in excitotoxic neuron death: cytochrome c release and a secondary increase in superoxide production. Mol Cancer. 2007 Dec 1;6:77.

The secondary rise could be inhibited by the complex I inhibitor rotenone (in combination with oligomycin) and mimicked by the complex III inhibitor antimycin A.
31(0,1,1,1) Details
17581813 Marella M, Seo BB, Matsuno-Yagi A, Yagi T: Mechanism of cell death caused by complex I defects in a rat dopaminergic cell line. Can J Microbiol. 2005 Aug;51(8):695-703.

We have shown that expression of a rotenone-insensitive yeast NADH-quinone oxidoreductase (Ndi1) can rescue mammalian cells from complex I dysfunction.
18(0,0,2,8) Details
17332151 Janssen AJ, Trijbels FJ, Sengers RC, Smeitink JA, van den Heuvel LP, Wintjes LT, Stoltenborg-Hogenkamp BJ, Rodenburg RJ: Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Brain Res. 2005 Jul 27;1051(1-2):25-34.

CONCLUSIONS: This spectrophotometric assay is reproducible, sensitive, and specific for complex I activity because of its high rotenone sensitivity, and it can be applied successfully to the diagnosis of complex I deficiencies.
13(0,0,1,8) Details
9377792 Ribeiro SM, Campello AP, Nascimento AJ, Kluppel ML: Effect of amiodarone (AMD) on the antioxidant enzymes, lipid peroxidation and mitochondrial metabolism. Cell Biochem Funct. 1997 Sep;15(3):145-52.

The results confirm the effects of AMD on complex I and permit the placing of this drug in class A of the classification of Knobeloch, together with rotenone, amytal and chaotropic agents.
6(0,0,1,1) Details
9625705 Bernhard Teicher H, Vibe Scheller H: The NAD (P) H dehydrogenase in barley thylakoids is photoactivatable and uses NADPH as well as NADH . Plant Physiol. 1998 Jun;117(2):525-32.

The enzyme was sensitive to rotenone, confirming the involvement of a complex I-type enzyme.
6(0,0,1,1) Details
9914819 Lenaz G, Cavazzoni M, Genova ML, D'Aurelio M, Merlo Pich M, Pallotti F, Formiggini G, Marchetti M, Parenti Castelli G, Bovina C: Oxidative stress, antioxidant defences and aging. Biochemistry. 2009 Jan;74(1):47-53.

Complex I activity and its rotenone sensitivity decreased in brain cortex non-synaptic mitochondria from old rats; a 5 kb mitochondrial DNA deletion was found only in the old rats.
6(0,0,1,1) Details
6513990 Takamiya S, Furushima R, Oya H: Electron transfer complexes of Ascaris suum muscle mitochondria: I. Mol Pharmacol. 1995 Nov;48(5):825-34.

Characterization of NADH-cytochrome c reductase (complex I-III), with special reference to cytochrome localization..
The enzyme preparation catalyzed the reduction of 1.68 mumol cytochrome c min-1 mg-1 protein at 25 degrees C with NADH but not with NADPH, and retained its sensitivity to rotenone, piericidin A and 2-heptyl-4-hydroxyquinoline-N-oxide as with the submitochondrial particles.
4(0,0,0,4) Details
10491161 Almeida T, Duarte M, Melo AM, Videira A: The 24-kDa iron-sulphur subunit of complex I is required for enzyme activity. Oncogene. 1999 Nov 4;18(46):6380-7.

In agreement with this, the respiration of intact mitochondria or mitochondrial membranes from the mutant strain is insensitive to rotenone inhibition.
4(0,0,0,4) Details
18485875 Martinvalet D, Dykxhoorn DM, Ferrini R, Lieberman J: Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death. Cell. 2008 May 16;133(4):681-92.

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16919272 Centonze D, Prosperetti C, Barone I, Rossi S, Picconi B, Tscherter A, De Chiara V, Bernardi G, Calabresi P: NR2B-containing NMDA receptors promote the neurotoxic effects of 3-nitropropionic acid but not of rotenone in the striatum. Exp Neurol. 2006 Dec;202(2):470-9. Epub 2006 Aug 17.

Decreased activity of mitochondrial complex I and II is implicated in the pathophysiology of progressive supranuclear palsy (PSP) and Huntington's disease (HD), respectively.
2(0,0,0,2) Details
17583437 Behrouz B, Drolet RE, Sayed ZA, Lookingland KJ, Goudreau JL: Unique responses to mitochondrial complex I inhibition in tuberoinfundibular dopamine neurons may impart resistance to toxic insult. J Biol Chem. 2005 Apr 22;280(16):15587-94. Epub 2005 Feb 14.

In the present experiments, direct exposure to rotenone or 1-methyl-4-phenylpyridinium (MPP+) had no effect on mediobasal hypothalamic TIDA neurons, but significantly increased the percentage of apoptag immunoreactive neurons in midbrain primary NSDA and MLDA cultures.
2(0,0,0,2) Details
1907569 Berger S, Ellersiek U, Steinmuller K: Cyanobacteria contain a mitochondrial complex I-homologous NADH-dehydrogenase. Toxicol Sci. 2009 Dec;112(2):427-34. Epub 2009 Sep 18.

Both membranes oxidize NADH in a rotenone-sensitive reaction.
2(0,0,0,2) Details
2174736 Modica-Napolitano JS, Joyal JL, Ara G, Oseroff AR, Aprille JR: Mitochondrial toxicity of cationic photosensitizers for photochemotherapy. Neurology. 1997 Jun;48(6):1623-32.

With photoirradiation VB-BO was also shown to inhibit rotenone-sensitive NADH-cytochrome c reductase activity, but it had no effect on succinate-cytochrome c reductase activity.
These data indicate that photoactivation of VB-BO produces selective inhibition of mitochondrial respiratory complex I.
2(0,0,0,2) Details
19250966 Mastroberardino PG, Hoffman EK, Horowitz MP, Betarbet R, Taylor G, Cheng D, Na HM, Gutekunst CA, Gearing M, Trojanowski JQ, Anderson M, Chu CT, Peng J, Greenamyre JT: A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson's disease. Neurobiol Dis. 2009 Jun;34(3):417-31. Epub 2009 Feb 26.

Importantly, the Tf/TfR2 pathway can deliver Tf bound iron to mitochondria and to the respiratory complex I as well.
In the rotenone model of PD, Tf accumulates in dopamine neurons, with much of it accumulating in the mitochondria.
1(0,0,0,1) Details
12399275 Madapallimattam AG, Law L, Jeejeebhoy KN: Effect of hypoenergetic feeding on muscle oxidative phosphorylation and mitochondrial complex I-IV activities in rats. Antioxid Redox Signal. 2007 Nov;9(11):1825-36.

RESULTS: A significant relation was observed between weight loss and the state 4 and 3 oxidation rates with pyruvate + malate and for state 3 glutamate + malate and succinate + rotenone but not with tetramethyl-p-phenylenediamine + ascorbate + antimycin A (TMPD).
1(0,0,0,1) Details
16416317 Igamberdiev AU, Shen T, Gardestrom P: Function of mitochondria during the transition of barley protoplasts from low light to high light. Biochim Biophys Acta. 1999 May 26;1412(1):56-65.

Rotenone (an inhibitor of mitochondrial complex I) had similar, but less pronounced effect as oligomycin.
Rotenone (an inhibitor of mitochondrial complex I) had similar, but less pronounced effect as oligomycin.
1(0,0,0,1) Details
1497658 Sivan VM, Raj RK: Quinone dependent NADH dehydrogenation in mitochondria-like particles from Setaria digitata, a filarial parasite. Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):826-33. Epub 2008 Apr 18.

In the cattle filarial parasite, Setaria digitata, the mitochondria-like particles have been shown to possess site I associated oxidative phosphorylation and rotenone sensitive and insensitive pathways for the dehydrogenation of NADH.
Thus activities of complex I and fumarate reductase are linked to quinone.
1(0,0,0,1) Details
17291988 Wang QS, Zheng YM, Dong L, Ho YS, Guo Z, Wang YX: Role of mitochondrial reactive oxygen species in hypoxia-dependent increase in intracellular calcium in pulmonary artery myocytes. Sheng Li Xue Bao. 2006 Oct 25;58(5):421-8.

Here we report that in freshly isolated mouse PASMCs, which are devoid of the mixed responses from multi-types of cells in lungs and significant changes in gene expression in cultured cells, the mitochondrial electron transport chain (ETC) complex I, II, or III inhibitors blocked hypoxia-induced increases in intracellular ROS and Ca2+ concentration ([ROS] i and [Ca2+] i) without effects on their resting levels.
Moreover, H2O2 (5.1 microM) reversed the inhibition of the hypoxia-induced increase in [Ca2+] i by rotenone.
1(0,0,0,1) Details
19860724 Agnati FL, Guidolin D, Baluska F, Leo G, Barlow PW, Carone C, Genedani S: A New Hypothesis of Pathogenesis Based on the Divorce between Mitochondria and their Host Cells: Possible Relevances for the Alzheimer's Disease. Bioorg Med Chem Lett. 2009 Feb 1;19(3):972-5. Epub 2008 Nov 24.

As a matter of fact, alpha-syn can enter mitochondria and interact with complex I causing respiratory deficiency and increased oxygen free radical production.
This proposal finds indirect support from observations on rotenone-poisoned glioblastoma cells which have been co-cultured with non-poisoned cells.
1(0,0,0,1) Details
19114648 Chan SH, Wu KL, Chang AY, Tai MH, Chan JY: Oxidative impairment of mitochondrial electron transport chain complexes in rostral ventrolateral medulla contributes to neurogenic hypertension. Hypertension. 2009 Feb;53(2):217-27. Epub 2008 Dec 29.

This mobile electron carrier also antagonized the elevated H (2) O (2) in RVLM and vasopressor responses to complex I (rotenone) or III (antimycin A) inhibitor in Wistar-Kyoto or prehypertensive rats.
81(1,1,1,1) Details
16667685 Pascal N, Dumas R, Douce R: Comparison of the Kinetic Behavior toward Pyridine Nucleotides of NAD-Linked Dehydrogenases from Plant Mitochondria. Biofizika. 2000 Jul-Aug;45(4):695-9.

It is suggested that NAD (+)-linked malic enzyme, when fully activated, is able to raise the matricial NADH level up to the required concentration to fully engage the rotenone-resistant internal NADH-dehydrogenase, whose affinity for NADH is weaker than complex I.
81(1,1,1,1) Details
11431129 Schuchmann S, Kovacs R, Kann O, Heinemann U, Buchheim K: Monitoring NAD (P) H autofluorescence to assess mitochondrial metabolic functions in rat hippocampal-entorhinal cortex slices. Behav Brain Res. 2004 Aug 31;153(2):439-46.

In contrast, the increase in NAD (P) H signal that followed a brief inhibition of mitochondrial respiratory chain complex I using rotenone (1 microM) indicated an accumulation of NAD (P) H.
81(1,1,1,1) Details
15845907 Basta G, Lazzerini G, Del Turco S, Ratto GM, Schmidt AM, De Caterina R: At least 2 distinct pathways generating reactive oxygen species mediate vascular cell adhesion molecule-1 induction by advanced glycation end products. Toxicol Appl Pharmacol. 1997 Jul;145(1):74-81.

The inhibition of NAD (P) H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively.
81(1,1,1,1) Details
20117074 Tocilescu MA, Fendel U, Zwicker K, Drose S, Kerscher S, Brandt U: The role of a conserved tyrosine in the 49-kDa subunit of complex I for ubiquinone binding and reduction. Biochim Biophys Acta. 2010 Feb 1.

Apparent K (m) values for Q (1) and Q (2) were markedly increased and we found pronounced resistance to the complex I inhibitors decyl-quinazoline-amine (DQA) and rotenone.
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12231169 Seo BB, Nakamaru-Ogiso E, Flotte TR, Yagi T, Matsuno-Yagi A: A single-subunit NADH-quinone oxidoreductase renders resistance to mammalian nerve cells against complex I inhibition. Mol Gen Genet. 1996 Aug 27;252(1-2):177-83.

The cells expressing the Ndi1 protein were resistant to known inhibitors of complex I, such as rotenone and pyridaben.
36(0,1,1,6) Details
7503762 Wyatt KM, Skene C, Veitch K, Hue L, McCormack JG: The antianginal agent ranolazine is a weak inhibitor of the respiratory complex I, but with greater potency in broken or uncoupled than in coupled mitochondria. Biochem Pharmacol. 1995 Nov 9;50(10):1599-606.

Studies with different electron acceptors and respiratory inhibitors indicated that it inhibits respiratory Complex I at a site between ferricyanide and menadione and ubiquinone-1 reduction (i.e. at a similar locus to rotenone).
33(0,1,1,3) Details
11689167 King TD, Bijur GN, Jope RS: Caspase-3 activation induced by inhibition of mitochondrial complex I is facilitated by glycogen synthase kinase-3beta and attenuated by lithium. Arch Biochem Biophys. 1996 May 15;329(2):145-55.

To test if these regulatory interactions applied to other mitochondrial complex I inhibitors, cells were treated with rotenone.
33(0,1,1,3) Details
14715437 Xu G, Perez-Pinzon MA, Sick TJ: Mitochondrial complex I inhibition produces selective damage to hippocampal subfield CA1 in organotypic slice cultures. Neurotox Res. 2003;5(7):529-38.

Slice cultures, 2-3 week old, were exposed for 1 h to either the Complex I inhibitors, rotenone or 1-methyl-4-phenylpyridium (MPP+), the Complex II inhibitor 3-nitropropionic acid (3-NP), or the excitotoxin NMDA.
32(0,1,1,2) Details
12437580 Wang X, Qin ZH, Leng Y, Wang Y, Jin X, Chase TN, Bennett MC: Prostaglandin A1 inhibits rotenone-induced apoptosis in SH-SY5Y cells. J Neurosci. 2003 Nov 26;23(34):10756-64.

To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A1 (PGA1), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH-SY5Y cells to the complex I inhibitor rotenone.
32(0,1,1,2) Details
9225812 Fujibayashi Y, Taniuchi H, Yonekura Y, Ohtani H, Konishi J, Yokoyama A: Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential. J Biol Chem. 1986 Mar 5;261(7):3068-74.

As a model of hypoxic mitochondria, rotenone (Complex I inhibitor)-treated mitochondria were used.
31(0,1,1,1) Details
14743397 Shih CM, Ko WC, Wu JS, Wei YH, Wang LF, Chang EE, Lo TY, Cheng HH, Chen CT: Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. Curr Neuropharmacol. 2006 Jan;4(1):69-75.

Using inhibitors of the mitochondrial electron transport chain (ETC) (oligomycin A and rotenone for complex I and V, respectively) and mitochondrial permeability transition pore (MPTP) (cyclosporin A and aristolochic acid), we coincidently found the ROS production, mitochondrial membrane depolarization, and apoptotic content were almost completely or partially abolished.
31(0,1,1,1) Details
18522491 Wenzel P, Mollnau H, Oelze M, Schulz E, Wickramanayake JM, Muller J, Schuhmacher S, Hortmann M, Baldus S, Gori T, Brandes RP, Munzel T, Daiber A: First evidence for a crosstalk between mitochondrial and NADPH oxidase-derived reactive oxygen species in nitroglycerin-triggered vascular dysfunction. Clin Chim Acta. 2006 Dec;374(1-2):81-6. Epub 2006 Jun 2.

Vice versa, nitrate tolerance was attenuated by co-treatment with the respiratory chain complex I inhibitor rotenone (100 microg/h/4 day) or the mitochondrial permeability transition pore blocker cyclosporine A (50 microg/h/4 day).
31(0,1,1,1) Details
14550906 Orth M, Tabrizi SJ, Schapira AH, Cooper JM: Alpha-synuclein expression in HEK293 cells enhances the mitochondrial sensitivity to rotenone. J Biol Chem. 2005 Jul 15;280(28):25994-6001. Epub 2005 Apr 22.

However, both wild-type and mutant G209A alpha-synuclein expression enhanced the fall in mitochondrial membrane potential induced by the complex I inhibitor rotenone.
31(0,1,1,1) Details
7566122 Jouaville LS, Ichas F, Holmuhamedov EL, Camacho P, Lechleiter JD: Synchronization of calcium waves by mitochondrial substrates in Xenopus laevis oocytes. J Neurosci. 2005 Oct 26;25(43):10029-40.

The effects of pyruvate/malate are blocked by ruthenium red at the Ca2+ uniporter, by rotenone at complex I, and by antimycin A at complex III, and are subsequently rescued at complex IV by ascorbate tetramethylphenylenediamine (TMPD).
31(0,1,1,1) Details
10597238 Suzuki S, Higuchi M, Proske RJ, Oridate N, Hong WK, Lotan R: Implication of mitochondria-derived reactive oxygen species, cytochrome C and caspase-3 in N-(4-hydroxyphenyl) retinamide-induced apoptosis in cervical carcinoma cells. J Biol Chem. 1996 Jun 21;271(25):14785-90.

Rotenone, an MRC complex I inhibitor was less effective and azide, an MRC complex IV inhibitor, exhibited a marginal effect.
31(0,1,1,1) Details
9689052 Seo BB, Kitajima-Ihara T, Chan EK, Scheffler IE, Matsuno-Yagi A, Yagi T: Molecular remedy of complex I defects: rotenone-insensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae mitochondria restores the NADH oxidase activity of complex I-deficient mammalian cells. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9167-71.
12(0,0,2,2) Details
15849190 Pineau B, Mathieu C, Gerard-Hirne C, De Paepe R, Chetrit P: Targeting the NAD7 subunit to mitochondria restores a functional complex I and a wild type phenotype in the Nicotiana sylvestris CMS II mutant lacking nad7. Physiol Plant. 2007 Dec;131(4):527-41.

CMSII plants lack rotenone-sensitive complex I activity and are impaired in physiological and phenotypical traits.
12(0,0,1,7) Details
15450959 Cardol P, Vanrobaeys F, Devreese B, Van Beeumen J, Matagne RF, Remacle C: Higher plant-like subunit composition of mitochondrial complex I from Chlamydomonas reinhardtii: 31 conserved components among eukaryotes. Neurosci Lett. 2002 Jun 28;326(2):97-100.

The rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) is the most intricate membrane-bound enzyme of the mitochondrial respiratory chain.
12(0,0,1,7) Details
18957561 de Wit LE, Scholte HR, Sluiter W: Correct assay of complex I activity in human skin fibroblasts by timely addition of rotenone. Clin Chem. 2008 Nov;54(11):1921-2; author reply 1922-4.
6(0,0,1,1) Details
16828729 Benit P, Goncalves S, Philippe Dassa E, Briere JJ, Martin G, Rustin P: Three spectrophotometric assays for the measurement of the five respiratory chain complexes in minuscule biological samples. Genetics. 2001 Jul;158(3):1051-60.

A third assay measures rotenone-sensitive complex I activity and subsequently oligomycin-sensitive complex V activity.
6(0,0,1,1) Details
8546703 Degli Esposti M, Ngo A, McMullen GL, Ghelli A, Sparla F, Benelli B, Ratta M, Linnane AW: The specificity of mitochondrial complex I for ubiquinones. J Cell Biochem. 2000 Oct 20;80(2):216-22.

The rate of NADH:Q reductase activity is potently but incompletely inhibited by rotenone, and the residual rotenone-insensitive rate is stimulated by Q analogues in different ways depending on the hydrophobicity of their substituent.
6(0,0,0,6) Details
19047048 Porcelli AM, Angelin A, Ghelli A, Mariani E, Martinuzzi A, Carelli V, Petronilli V, Bernardi P, Rugolo M: Respiratory complex I dysfunction due to mitochondrial DNA mutations shifts the voltage threshold for opening of the permeability transition pore toward resting levels. Eur J Pharmacol. 1995 Jul 14;280(3):251-6.

The addition of rotenone to HL180 cells and of antimycin A to XTC.UC1 cells caused fast mitochondrial membrane depolarization that was prevented by treatment with cyclosporin A, intracellular Ca2+ chelators, and antioxidant.
4(0,0,0,4) Details
19433311 Plecita-Hlavata L, Jezek J, Jezek P: Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I. Neurosci Lett. 2006 Apr 10-17;397(1-2):69-73. Epub 2006 Jan 10.

In rotenone-inhibited HepG2 cells (i.e., already under oxidative stress) MitoQ (10) sharply decreased rotenone-induced J (m), but not together with the Complex II inhibitor thenoyltrifluoroacetone.
4(0,0,0,4) Details
19366681 Hoffman DL, Brookes PS: Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions. Biochem Pharmacol. 1995 May 11;49(9):1303-11.


From such data, the apparent Km for O2 of putative ROS-generating sites within mitochondria was estimated as follows: 0.2, 0.9, 2.0, and 5.0 microM O2 for the complex I flavin site, complex I electron backflow, complex III QO site, and electron transfer flavoprotein quinone oxidoreductase of beta-oxidation, respectively.
2(0,0,0,2) Details
8898917 Rigoulet M, Devin A, Averet N, Vandais B, Guerin B: Mechanisms of inhibition and uncoupling of respiration in isolated rat liver mitochondria by the general anesthetic 2,6-diisopropylphenol. Biochim Biophys Acta. 1997 Jan 16;1318(1-2):246-54.


Diisopropylphenol strongly inhibits state-3 and uncoupled respiratory rates, when glutamate and malate are the substrates, as a direct consequence of the limitation of electron transfer at the level of complex I.
2(0,0,0,2) Details
10371218 Braidot E, Petrussa E, Vianello A, Macri F: Hydrogen peroxide generation by higher plant mitochondria oxidizing complex I or complex II substrates. Nucl Med Biol. 1995 Jan;22(1):65-9.

The succinate-dependent H2O2 formation was abolished by malonate, but unaffected by rotenone.
2(0,0,0,2) Details
15084427 Alam M, Mayerhofer A, Schmidt WJ: The neurobehavioral changes induced by bilateral rotenone lesion in medial forebrain bundle of rats are reversed by L-DOPA. 131-40.

Rotenone (an inhibitor of mitochondrial complex I) has been proposed as a model of Parkinson's disease (PD) as it induces nigrostriatal degeneration associated with alpha-synuclein inclusions.
1(0,0,0,1) Details
10917647 Ohnishi T, Magnitsky S, Toulokhonova L, Yano T, Yagi T, Burbaev DS, Vinogradov AD, Sled VD: EPR studies of the possible binding sites of the cluster N2, semiquinones, and specific inhibitors of the NADH:quinone oxidoreductase (complex I). Brain Res. 2001 May 4;900(1):72-9.

1(0,0,0,1) Details
19245829 Tahara EB, Navarete FD, Kowaltowski AJ: Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation. Biochem J. 1996 Jan 1;313 ( Pt 1):327-34.

The locations and properties of reactive oxygen species formation were determined using oxidative phosphorylation and the respiratory chain modulators oligomycin, rotenone, myxothiazol, and antimycin A and the uncoupler CCCP.
Our findings support an important participation of flavoenzymes and complex III and a substantial role for reverse electron transport to complex I as reactive oxygen species sources.
1(0,0,0,1) Details
19562601 Henderson JR, Swalwell H, Boulton S, Manning P, McNeil CJ, Birch-Machin MA: Direct, real-time monitoring of superoxide generation in isolated mitochondria. Diabetologia. 2005 Mar;48(3):586-94. Epub 2005 Feb 24.


The non-invasive sensor system described allowed a comparison of [image omitted] production following specific inhibition of complex I and complex III of the mETC to be made directly and in real-time.
1(0,0,0,1) Details
12736522 Xu ZF, Wei XY, Xie HH, Yang RZ: Inhibitory activities of three annonaceous acetogenins on NADH oxidase of chicken liver mitochondria. J Neurochem. 1999 Jul;73(1):220-8.

Annonaceous acetogenins (ACG) are natural products found in the plant family Annonaceae and which strongly inhibited mitochondrial complex I.
The inhibition of NADH oxidase of chicken liver mitochondria by three different structural ACG was studied here, and ACG was shown to have potent inhibitory activities similar to rotenone for NADH oxidase.
1(0,0,0,1) Details
18298370 Isaev NK, Stelmashook EV, Dirnagl U, Plotnikov EY, Kuvshinova EA, Zorov DB: Mitochondrial free radical production induced by glucose deprivation in cerebellar granule neurons. Biochemistry. 2008 Feb;73(2):149-55.

Inhibitors of mitochondrial electron transport, i.e. rotenone (complex I), antimycin A (complex III), or sodium azide (complex IV), an inhibitor of mitochondrial ATP synthase--oligomycin, an uncoupler of oxidative phosphorylation--CCCP, a chelator of intracellular Ca2+--BAPTA, an inhibitor of electrogenic mitochondrial Ca2+ transport--ruthenium red, as well as pyruvate significantly decreased neuronal ROS production induced by GD.
81(1,1,1,1) Details
15941011 Terzi A, Iraz M, Sahin S, Ilhan A, Idiz N, Fadillioglu E: Protective effects of erdosteine on rotenone-induced oxidant injury in liver tissue. Toxicol Ind Health. 2004 Sep;20(6-10):141-7.

Rotenone, an insecticide of botanical origin, causes toxicity through inhibition of complex I of the respiratory chain in mitochondria.
81(1,1,1,1) Details
15557194 Woo CH, Lim JH, Kim JH: Lipopolysaccharide induces matrix metalloproteinase-9 expression via a mitochondrial reactive oxygen species-p38 kinase-activator protein-1 pathway in Raw 264.7 cells. Mol Biol Rep. 2008 Sep;35(3):397-403. Epub 2007 May 26.

LPS-induced MMP-9 expression and p38 kinase phosphorylation were also inhibited by rotenone, a specific inhibitor of mitochondrial complex I, supporting the role of mitochondrial ROS in LPS signaling to MMP-9.
81(1,1,1,1) Details
19707849 Moldzio R, Radad K, Krewenka C, Kranner B, Duvigneau JC, Wang Y, Rausch WD: Effects of epigallocatechin gallate on rotenone-injured murine brain cultures. FEBS Lett. 2005 Jul 18;579(18):4005-11.

Rotenone is a potent inhibitor of complex I of the respiratory chain, which in vitro causes pathological and neurochemical characteristics of diseases in which mitochondrial impairment is involved, e.g., Parkinson's disease.
81(1,1,1,1) Details
16687518 Keeney PM, Xie J, Capaldi RA, Bennett JP Jr: Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. Free Radic Res. 2009 Sep;43(9):796-802. Epub 2009 Jun 25.

This complex I auto-oxidation may derive from abnormalities in mitochondrial or nuclear encoded subunits, complex I assembly factors, rotenone-like complex I toxins, or some combination.
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19096098 Fato R, Bergamini C, Leoni S, Lenaz G: Mitochondrial production of reactive oxygen species: role of complex I and quinone analogues. Neurochem Res. 2005 Sep;30(9):1191-200.

The presence of specific inhibitors modulates reactive oxygen species production in Complex I: inhibitors such as rotenone induce a strong ROS increase, while inhibitors such as stigmatellin prevent it.
36(0,1,1,6) Details
10097178 Schuler F, Yano T, Di Bernardo S, Yagi T, Yankovskaya V, Singer TP, Casida JE: NADH-quinone oxidoreductase: PSST subunit couples electron transfer from iron-sulfur cluster N2 to quinone. Brain Res. 2001 Nov 16;919(1):106-14.

Complex I and NDH-1 are very sensitive to inhibition by a variety of structurally diverse toxicants, including rotenone, piericidin A, bullatacin, and pyridaben.
33(0,1,1,3) Details
16120400 Cameron JM, Levandovskiy V, MacKay N, Robinson BH: Respiratory chain analysis of skin fibroblasts in mitochondrial disease. . J Clin Invest. 1987 Jul;80(1):71-7.

NADH:ubiquinone dehydrogenase (complex I) deficiency can be diagnosed from cultured skin fibroblasts using a number of methods, the most commonly used is a linked assay of rotenone-sensitive complex I + III activity (NADH:cytochrome c reductase).
33(0,1,1,3) Details
1753716 Lamperth L, Dalakas MC, Dagani F, Anderson J, Ferrari R: Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model. Curr Med Chem. 2003 Dec;10(23):2507-16.

Study of the mitochondrial functions assessed by evaluating stimulated oxygen consumption rate, enzymatic activities of electron transport chain and coupling state of oxidative phosphorylation (respiratory control ratio) revealed a decrease in rotenone-sensitive NADH cytochrome C reductase (complex I + III) and an uncoupling effect demonstrated by decreased respiratory control ratio.
32(0,1,1,2) Details
16699582 Chen Y, Suzuki I: Electron transport pathways for the oxidation of endogenous substrate (s) in Acidithiobacillus ferrooxidans. Lab Invest. 1991 Dec;65(6):742-51.

The oxidation was inhibited by complex I inhibitors (rotenone, amytal, and piericidin A) only partially, but piericidin A inhibited the oxidation with Fe3+ nearly completely.
32(0,1,1,2) Details
16410252 Moreira PI, Custodio J, Moreno A, Oliveira CR, Santos MS: Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure. Oncogene. 2000 Aug 10;19(34):3840-8.

Furthermore, using two respiratory chain inhibitors, rotenone and diphenyliodonium chloride, we identified the flavin mononucleotide site of complex I as the target of tamoxifen and/or estradiol action (s).
32(0,1,1,2) Details
15515888 Fujita K, Tani K, Usuki Y, Tanaka T, Taniguchi M: Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisiae. J Neurochem. 1992 Aug;59(2):746-9.

The addition of both a complex I inhibitor rotenone and a complex II inhibitor thenoyltrifluoroacetone reduced ROS generation induced by C9-UK-2A in the whole cells and the isolated mitochondria.
31(0,1,1,1) Details
20349346 Fujita Y, Hosokawa M, Fujimoto S, Mukai E, Abudukadier A, Obara A, Ogura M, Nakamura Y, Toyoda K, Nagashima K, Seino Y, Inagaki N: Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice. Diabetologia. 2010 Mar 29.

Since metformin is a mild mitochondrial complex I inhibitor, we compared its effects on suppression of gluconeogenesis, AMPK activation and generation of the RNS peroxynitrite (ONOO (-)) with those of rotenone, a representative complex I inhibitor.
31(0,1,1,1) Details
9305406 Klohn PC, Neumann HG: Impairment of respiration and oxidative phosphorylation by redox cyclers 2-nitrosofluorene and menadione. Biochim Biophys Acta. 1999 Jan 5;1409(3):143-53.

NOF reacts with the NADH:ubiquinone oxidoreductase (complex I) and consumes oxygen in a rotenone-insensitive manner.
31(0,1,1,1) Details
15000895 Zhang HX, Du GH, Zhang JT: Assay of mitochondrial functions by resazurin in vitro. PLoS One. 2009 Sep 18;4(9):e7100.

However, the typical complex I inhibitor, rotenone enhanced the fluorescence intensity without mitochondria.
31(0,1,1,1) Details
8892026 Pitkanen S, Feigenbaum A, Laframboise R, Robinson BH: NADH-coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings. J Biol Chem. 2003 Mar 7;278(10):8516-25. Epub 2002 Dec 20.

Each patient also had decreased rotenone-sensitive NADH-cytochrome c reductase (complexes I and III) with normal succinate cytochrome c reductase (complexes II and III) and cytochrome oxidase (complex IV) activity in cultured skin fibroblasts, indicating a deficient NADH-coenzyme Q reductase (complex I) activity.
31(0,1,1,1) Details
15268949 Chen Y, Suzuki I: Effect of uncouplers on endogenous respiration and ferrous iron oxidation in a chemolithoautotrophic bacterium Acidithiobacillus (Thiobacillus) ferrooxidans. J Bioenerg Biomembr. 2008 Aug;40(4):297-305. Epub 2008 Sep 17.

Complex I inhibitors, atabrine, rotenone and amytal inhibited Fe2+ oxidation, more strongly in the presence of 0.1 mM DNP.
31(0,1,1,1) Details
19196431 Guglielmotto M, Aragno M, Autelli R, Giliberto L, Novo E, Colombatto S, Danni O, Parola M, Smith MA, Perry G, Tamagno E, Tabaton M: The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1alpha. Mol Ther. 2002 Sep;6(3):336-41.

The involvement of reactive oxygen species released by mitochondria in the BACE1 up-regulation was confirmed by the complete protection exerted by complex I inhibitors such as rotenone and diphenyl-phenylen iodonium.
31(0,1,1,1) Details
17600838 Tretter L, Takacs K, Kover K, Adam-Vizi V: Stimulation of H (2) O (2) generation by calcium in brain mitochondria respiring on alpha-glycerophosphate. IUBMB Life. 2001 Apr;51(4):263-8.

In those mitochondria where RET was eliminated by the Complex I inhibitor rotenone (2 microM) or due to depolarization by ADP (1 mM), the rate of H (2) O (2) formation was smaller and the stimulation of H (2) O (2) generation by Ca (2+) was prevented partly, but the stimulatory effect of Ca (2+) was still significant.
31(0,1,1,1) Details
14962977 Ruan Q, Lesort M, MacDonald ME, Johnson GV: Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway. Neurochem Int. 2007 Jan;50(1):189-95. Epub 2006 Sep 8.

In contrast, the extent of cell death induced by rotenone, a complex I inhibitor, was similar in both cell lines.
31(0,1,1,1) Details
7873673 Maklashina EO, Vinogradov AD: [Participation of the quinone acceptor in the transition of complex I from an inactive to active state]. J Cell Biochem. 2004 Feb 1;91(2):384-97.

The rotenone-sensitive NADH oxidase was reconstituted from bovine heart Complex I and Escherichia coli quinol-oxidase.
11(0,0,1,6) Details
10702521 Brooks H, Krahenbuhl S: Development of a new assay for complex I of the respiratory chain. J Biol Chem. 2009 Jun 12;284(24):16236-45. Epub 2009 Apr 14.

Sensitivity to rotenone was used as a measure of complex I specific activity.
11(0,0,1,6) Details
12627969 Peng G, Fritzsch G, Zickermann V, Schagger H, Mentele R, Lottspeich F, Bostina M, Radermacher M, Huber R, Stetter KO, Michel H: Isolation, characterization and electron microscopic single particle analysis of the NADH:ubiquinone oxidoreductase (complex I) from the hyperthermophilic eubacterium Aquifex aeolicus. J Neurochem. 1996 Mar;66(3):1174-81.

The A. aeolicus complex I is completely sensitive to rotenone and 2-n-decyl-quinazoline-4-yl-amine.
11(0,0,1,6) Details
15763667 Mariano AB, Valente C, Cadena SM, Rocha ME, de Oliveira MB, Carnieri EG: Sensitivities of the alternative respiratory components of potato tuber mitochondria to thiol reagents and Ca2+. BMC Neurosci. 2008 Jan 8;9:4.

Another feature of plant mitochondria is that besides complex I (EC 1.6.5.3) they possess alternative NAD (P) H-dehydrogenases insensitive to rotenone.
6(0,0,1,1) Details
18291703 Dlaskova A, Hlavata L, Jezek P: Oxidative stress caused by blocking of mitochondrial complex I H (+) pumping as a link in aging/disease vicious cycle. Am J Physiol Cell Physiol. 2008 May;294(5):C1124-32. Epub 2008 Mar 19.

Rotenone caused a 5-fold J (m) increase (AC (50) 2 microM), which was attenuated by uncoupling, membrane potential (DeltaPsi (m)), and DeltapH-collapse, since addition of FCCP (IC (50) 55 nM), valinomycin, and nigericin prevented this increase.
6(0,0,0,6) Details
1904460 Harbord MG, Hwang PA, Robinson BH, Becker LE, Hunjan A, Murphy EG: Infant-onset progressive myoclonus epilepsy. . Biochem Pharmacol. 1996 Jun 14;51(11):1503-11.

Respiratory-chain enzyme studies were performed on five samples and in three children (all of whom had a history of elevated lactate in serum or cerebrospinal fluid), there were low levels of rotenone-sensitive reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase characteristic of a defect in the complex I part of the respiratory-chain pathway.
6(0,0,1,1) Details
9733090 Barja G, Herrero A: Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon. J Biol Chem. 2003 Sep 26;278(39):37948-56. Epub 2003 Jul 3.

Rotenone, antimycin A, and myxothiazol maximally stimulated free radical production with pyruvate/malate but not with succinate.
3(0,0,0,3) Details
215123 Heron C, Ragan CI, Trumpower BL: The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Biochem J. 1978 Sep 15;174(3):791-800.


Such behaviour can be restored to the interaction between purified Complex I and Complex III by addition of phospholipid and ubiquinone-10 to a concentrated mixture of the Complexes before dilution. 3.
3(0,0,0,3) Details
8535408 Taniuchi H, Fujibayashi Y, Okazawa H, Yonekura Y, Konishi J, Yokoyama A: Cu-pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), a metal complex with selective NADH-dependent reduction by complex I in brain mitochondria: a potential radiopharmaceutical for mitochondria-functional imaging with positron emission tomography (PET). Biol Pharm Bull. 1995 Aug;18(8):1126-9.

Rotenone and antimycin A activated the reduction of Cu-PTSM in the brain mitochondria by 1.6- and 1.4-fold, respectively, compared with untreated controls, while thenoyltrifluoroacetone (TTFA) had no effect on the reduction.
2(0,0,0,2) Details
15377162 Meyer MJ, Mosely DE, Amarnath V, Picklo MJ Sr: Metabolism of 4-hydroxy-trans-2-nonenal by central nervous system mitochondria is dependent on age and NAD+ availability. Biochemistry. 2006 Aug 15;45(32):9778-87.

Complex I inhibition with respiratory substrates further blocked HNE detoxification.
Rotenone (100 nM) inhibited respiration by 15% whereas HNEAcid formation was decreased to 72% of control levels.
2(0,0,0,2) Details
15465329 Andreani A, Granaiola M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Recanatini M, Lenaz G, Fato R, Bergamini C: Effects of new ubiquinone-imidazo [2,1-b] thiazoles on mitochondrial complex I (NADH-ubiquinone reductase) and on mitochondrial permeability transition pore. Eur J Biochem. 1983 Dec 1;137(1-2):113-8.

Moreover the low rotenone sensitivity for almost all of these compounds suggests that they are only partially able to interact with the physiological ubiquinone-reduction site.
2(0,0,0,2) Details
8216312 Debise R, Touraille S, Durand R, Alziari S: Biochemical consequences of a large deletion in the mitochondrial genome of a Drosophila subobscura strain. Free Radic Biol Med. 1994 Aug;17(2):117-26.


Spectrophotometric determination of respiratory complex activities shows that: complex I (5 genes implicated in deletion) presents maximal activity reduced by 40%, whereas that of complex III (concerned by cytochrome b) is lowered by 30%.
2(0,0,0,2) Details
12517982 Blackstone NW: Redox signaling in the growth and development of colonial hydroids. Clin Chem. 2007 Apr;53(4):729-34. Epub 2007 Mar 1.

Oxygen uptake of colonies was measured to determine comparable physiological doses of antimycin A (1) (an inhibitor of complex III), rotenone (an inhibitor of complex I) and carbonyl cyanide m-chlorophenylhydrazone (CCCP; an uncoupler of oxidative phosphorylation).
Oxygen uptake of colonies was measured to determine comparable physiological doses of antimycin A (1) (an inhibitor of complex III), rotenone (an inhibitor of complex I) and carbonyl cyanide m-chlorophenylhydrazone (CCCP; an uncoupler of oxidative phosphorylation).
2(0,0,0,2) Details
8603732 Merlo Pich M, Bovina C, Formiggini G, Cometti GG, Ghelli A, Parenti Castelli G, Genova ML, Marchetti M, Semeraro S, Lenaz G: Inhibitor sensitivity of respiratory complex I in human platelets: a possible biomarker of ageing. Behav Brain Res. 2004 May 5;151(1-2):117-24.

The enzyme activities were not significantly changed in the two groups, but a decrease of sensitivity to the specific inhibitor, rotenone, occurred in a substantial number of aged individuals.
1(0,0,0,1) Details
17533645 Annunen-Rasila J, Ohlmeier S, Tuokko H, Veijola J, Majamaa K: Proteome and cytoskeleton responses in osteosarcoma cells with reduced OXPHOS activity. J Toxicol Environ Health A. 2006 Sep;69(18):1681-97.


We describe here the cellular responses to OXPHOS deficiency in osteosarcoma cells upon complex I (CI) and complex IV (CIV) inhibition, and upon the lack of mitochondrial DNA (rho0 cells).
1(0,0,0,1) Details
17050618 Sridharan V, Guichard J, Bailey RM, Kasiganesan H, Beeson C, Wright GL: The prolyl hydroxylase oxygen-sensing pathway is cytoprotective and allows maintenance of mitochondrial membrane potential during metabolic inhibition. Biochem Int. 1990 Oct;22(2):303-9.

Thus, continued complex I activity was implicated in the maintenance of DeltaPsi (mito) in PHI-treated myocytes, whereas a role for the "reverse mode" operation of the F (1) F (0)-ATP synthase was ruled out.
Inclusion of rotenone, but not oligomycin, with cyanide and 2-DG was found to collapse DeltaPsi (mito) in PHI-pretreated myocytes.
1(0,0,0,1) Details
6536673 Landi L, Pasquali P, Cabrini L, Sechi AM, Lenaz G: On the mechanism of inhibition of NADH oxidase by ubiquinone-3. Am J Physiol Cell Physiol. 2007 Feb;292(2):C719-28. Epub 2006 Oct 18.

The combined effects of rotenone and ubiquinone-3 on the kinetics of NADH dehydrogenase and NADH oxidase have been investigated.
The inhibition of NADH oxidase by ubiquinone-3 is the result of at least two combined effects: the competition of the less active ubiquinone-3 with endogenous ubiquinone-10 in the acceptor site of the dehydrogenase, and a nonspecific action on the structure of complex I.
1(0,0,0,1) Details
12080052 Damdimopoulos AE, Miranda-Vizuete A, Pelto-Huikko M, Gustafsson JA, Spyrou G: Human mitochondrial thioredoxin. J Bioenerg Biomembr. 1984 Apr;16(2):153-66.

In addition, HEK-Trx2 are more sensitive toward rotenone, an inhibitor of complex I of the respiratory chain.
In addition, HEK-Trx2 are more sensitive toward rotenone, an inhibitor of complex I of the respiratory chain.
1(0,0,0,1) Details
11527152 Monti E, Supino R, Colleoni M, Costa B, Ravizza R, Gariboldi MB: Nitroxide TEMPOL impairs mitochondrial function and induces apoptosis in HL60 cells. J Neurosci. 2006 May 10;26(19):5256-64.


In addition, TEMPOL was found to specifically target complex I of the respiratory chain, with minor effects on complexes II and IV, suggesting that mitochondrial effects might play a role in TEMPOL-induced oxidative stress and apoptosis, and that TEMPOL might sensitize tumor cells to the pro-apoptotic effects of cytotoxic agents.
1(0,0,0,1) Details
10366439 Leist M, Single B, Naumann H, Fava E, Simon B, Kuhnle S, Nicotera P: Inhibition of mitochondrial ATP generation by nitric oxide switches apoptosis to necrosis. FEMS Immunol Med Microbiol. 1999 Jun;24(2):169-74.

In contrast, depleting intracellular ATP with rotenone, an inhibitor of mitochondrial complex I mimicked the effect of NO.
In contrast, depleting intracellular ATP with rotenone, an inhibitor of mitochondrial complex I mimicked the effect of NO.
1(0,0,0,1) Details
8663005 Rustin P, Parfait B, Chretien D, Bourgeron T, Djouadi F, Bastin J, Rotig A, Munnich A: Fluxes of nicotinamide adenine dinucleotides through mitochondrial membranes in human cultured cells. Arch Biochem Biophys. 2002 Sep 15;405(2):252-64.


They also point to the possible confusion between a loss of mitochondrial NAD and a defect of respiratory chain complex I in the context of screening procedures for respiratory chain disorder in human.
1(0,0,0,1) Details
12846980 Fiskum G, Starkov A, Polster BM, Chinopoulos C: Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson's disease. Mol Pharmacol. 2000 Aug;58(2):271-8.

Neurotoxins that induce parkinsonian neuropathology, such as MPP (+) and rotenone, stimulate superoxide production at complex I of the electron transport chain and also stimulate free radical production at proximal redox sites including mitochondrial matrix dehydrogenases.
81(1,1,1,1) Details
16659084 Tomlinson PF, Moreland DE: Cyanide-resistant Respiration of Sweet Potato Mitochondria. . Plant Physiol. 1975 Feb;55(2):365-369.

Essentially complete inhibition was obtained with inhibitors of complex I (rotenone, amytal, and thenoyltrifluoroacetone) and complex II (thenoyltrifluoroacetone).
81(1,1,1,1) Details
17210467 VanBrocklin HF, Hanrahan SM, Enas JD, Nandanan E, O'Neil JP: Mitochondrial avid radioprobes. J Neurochem. 1998 Dec;71(6):2549-57.

Two tracers, 7'-Z-iodorotenol and 7'-Z-iodorotenone, analogs of rotenone a natural product that inhibits Complex I of the mitochondrial electron transport chain, have been labeled with iodine-125 in 45-85% yield in a single step from the corresponding tributylstannyl precursor.
81(1,1,1,1) Details
19744517 Hosamani R, Muralidhara: Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. Synapse. 2003 Dec 1;50(3):240-50.

Environmental toxins like rotenone, a specific inhibitor of complex I is employed to increase oxidative stress mediated neuropathology and sporadic Parkinson's disease.
81(1,1,1,1) Details
19041852 Gieseler A, Schultze AT, Kupsch K, Haroon MF, Wolf G, Siemen D, Kreutzmann P: Inhibitory modulation of the mitochondrial permeability transition by minocycline. FEBS Lett. 2005 Dec 19;579(30):6716-20. Epub 2005 Nov 21.

Treatment of neuron-enriched cortical cultures with rotenone, a high affinity inhibitor of the mitochondrial complex I, resulted in a deregulation of the intracellular Ca2+-dynamics, as recorded by live cell imaging.
81(1,1,1,1) Details
19174508 Nguyen KT, Garcia-Chacon LE, Barrett JN, Barrett EF, David G: The Psi (m) depolarization that accompanies mitochondrial Ca2+ uptake is greater in mutant SOD1 than in wild-type mouse motor terminals. Brain Res. 1998 Oct 26;809(1):12-7.

Stimulation-induced Psi (m) depolarization and elevation of cytosolic [Ca (2+)] both increased when complex I of the ETC was partially inhibited by low concentrations of rotenone (25-50 nmol/l).
81(1,1,1,1) Details
10433118 Combettes B, Grienenberger JM: Analysis of wheat mitochondrial complex I purified by a one-step immunoaffinity chromatography. Neurochem Int. 2005 Jun;46(7):513-21.

The complex retained on the column proved to be a functional complex I, since the preparation showed NADH:duroquinone and NADH:FeK3 (CN) 6 reductase activities which were inhibited by rotenone.
36(0,1,1,6) Details
12535666 Chretien D, Benit P, Chol M, Lebon S, Rotig A, Munnich A, Rustin P: Assay of mitochondrial respiratory chain complex I in human lymphocytes and cultured skin fibroblasts. J Antibiot. 2004 Aug;57(8):511-7.

The procedure strongly reduces contaminating NADH:quinone oxidoreductase activity and permits measuring high rates of rotenone-sensitive complex I activity thanks to effective cell permeabilization.
35(0,1,1,5) Details
16893179 Murai M, Ichimaru N, Abe M, Nishioka T, Miyoshi H: Mode of inhibitory action of Deltalac-acetogenins, a new class of inhibitors of bovine heart mitochondrial complex I. Biochem Biophys Res Commun. 2003 Jan 31;301(1):222-4.

We have revealed that Deltalac-acetogenins, a new class of inhibitors of bovine heart mitochondrial complex I (NADH-ubiquinone oxidoreductase), act differently from ordinary inhibitors such as rotenone and piericidin A [Ichimaru et al. (2005) Biochemistry 44, 816-825].
35(0,1,1,5) Details
20170624 Grivennikova VG, Kareyeva AV, Vinogradov AD: What are the sources of hydrogen peroxide production by heart mitochondria?. Eur J Biochem. 1984 Jun 15;141(3):573-7.

NADH-supported hydrogen peroxide production by the rotenone-treated mitochondria devoid of a permeability barrier for H (2) O (2) diffusion by alamethicin treatment are only partially ( approximately 50%) sensitive to the Complex I NADH binding site-specific inhibitor, NADH-OH.
33(0,1,1,3) Details
18251845 Juszczuk IM, Flexas J, Szal B, Dabrowska Z, Ribas-Carbo M, Rychter AM: Effect of mitochondrial genome rearrangement on respiratory activity, photosynthesis, photorespiration and energy status of MSC16 cucumber (Cucumis sativus) mutant. J Neurochem. 2001 Oct;79(2):266-77.

Decreased respiratory capacity of complex I in MSC16 mitochondria was indicated by lower respiration rates of intact mitochondria with malate and by rotenone-inhibited NADH or malate oxidation in the presence of alamethicin.
33(0,1,1,3) Details
14592516 Tormo JR, Gallardo T, Peris E, Bermejo A, Cabedo N, Estornell E, Zafra-Polo MC, Cortes D: Inhibitory effects on mitochondrial complex I of semisynthetic mono-tetrahydrofuran acetogenin derivatives. Brain Res. 2005 Feb 8;1033(2):143-50.

Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.
32(0,1,1,2) Details
12210849 Tai KK, Truong DD: Activation of adenosine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: therapeutic implications for Parkinson's disease. Plant J. 2001 Oct;28(1):73-82.

Here we show that transient activation of ATP-sensitive potassium channels, a trigger in ischemic preconditioning signaling, confers protection in PC12 cells and SH-SY5Y cells against neurotoxic effect of rotenone and MPTP, mitochondrial complex I inhibitors that have been implicated in the pathogenesis of Parkinson's disease.
31(0,1,1,1) Details
10438663 Di Monte DA, Tokar I, Langston JW: Impaired glutamate clearance as a consequence of energy failure caused by MPP (+) in astrocytic cultures. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4149-53.

The effect of MPP (+) on glutamate clearance: (i) was accompanied by a decrease in cellular ATP; (ii) could be enhanced by withdrawing glucose from the incubation medium or by inhibiting glycolysis with 2-deoxyglucose, and (iii) could be reproduced using the mitochondrial complex I inhibitor rotenone.
31(0,1,1,1) Details
17520785 Yi PL, Tsai CH, Lu MK, Liu HJ, Chen YC, Chang FC: Interleukin-1beta mediates sleep alteration in rats with rotenone-induced parkinsonism. Int J Biochem Cell Biol. 2004 Jan;36(1):162-72.

DESIGN: We employed a long-term subcutaneous infusion of rotenone, a mitochondrial complex-I inhibitor, to induce a parkinsonism-like model in rats.
31(0,1,1,1) Details
19781600 Ahn SY, Choi YS, Koo HJ, Jeong JH, Park WH, Kim M, Piao Y, Pak YK: Mitochondrial dysfunction enhances the migration of vascular smooth muscles cells via suppression of Akt phosphorylation. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2009 Dec;26(6):1191-200.

Similarly, dideoxycytidine (ddC), the mtDNA replication inhibitor, or rotenone, OXPHOS complex I inhibitor, inhibited the insulin-mediated pAkt while increased pAMPK regardless of insulin.
31(0,1,1,1) Details
12065751 Waldmeier PC, Feldtrauer JJ, Qian T, Lemasters JJ: Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. BMC Plant Biol. 2004 May 12;4:8.

Using two newly developed microtiter plate assays, one measuring mitochondrial swelling from absorbance and the other measuring mitochondrial membrane potential from changes in safranin fluorescence, we show that NIM811 blocks the MPT induced by calcium and inorganic phosphate, alone or in combination with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the complex I inhibitor rotenone, and the prooxidant t-butylhydroperoxide.
31(0,1,1,1) Details
12807439 Jensen PJ, Alter BJ, O'Malley KL: Alpha-synuclein protects naive but not dbcAMP-treated dopaminergic cell types from 1-methyl-4-phenylpyridinium toxicity. Mol Cancer. 2004 Jul 12;3:19.

Similarly, alpha-synuclein protected cells from the complex I inhibitor rotenone and 3-nitroproprionic acid, a complex II inhibitor.
31(0,1,1,1) Details
1332758 Finel M, Skehel JM, Albracht SP, Fearnley IM, Walker JE: Resolution of NADH:ubiquinone oxidoreductase from bovine heart mitochondria into two subcomplexes, one of which contains the redox centers of the enzyme. J Bioenerg Biomembr. 2009 Aug;41(4):379-85. Epub 2009 Oct 10.

The line shapes of the EPR spectra of the Fe-S clusters are slightly broadened relative to spectra measured on complex I purified by conventional means, and the quinone reductase activity is insensitive to rotenone.
11(0,0,1,6) Details
12079358 Cardol P, Matagne RF, Remacle C: Impact of mutations affecting ND mitochondria-encoded subunits on the activity and assembly of complex I in Chlamydomonas. Neurochem Int. 2006 Jul;49(1):28-40. Epub 2006 Feb 21.

The mitochondrial rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) comprises more than 35 subunits, the majority of which are encoded by the nucleus.
11(0,0,1,6) Details
11229440 Goossens V, Stange G, Moens K, Pipeleers D, Grooten J: Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I. Neuroscience. 2003;121(2):287-96.

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19097788 Dong CK, Patel V, Yang JC, Dvorin JD, Duraisingh MT, Clardy J, Wirth DF: Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors. J Biol Chem. 2004 Apr 23;279(17):17197-204. Epub 2004 Feb 11.

Plasmodium falciparum NDH2 (pfNDH2) is a non-proton pumping, rotenone-insensitive alternative enzyme to the multi-subunit NADH:ubiquinone oxidoreductases (Complex I) of many other eukaryotes.
6(0,0,1,1) Details
15047621 Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhausl W, Furnsinn C: Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?. Biochem Pharmacol. 2009 Mar 1;77(5):888-96. Epub 2008 Nov 12.

6(0,0,0,6) Details
9375690 Davey GP, Canevari L, Clark JB: Threshold effects in synaptosomal and nonsynaptic mitochondria from hippocampal CA1 and paramedian neocortex brain regions. J Neurochem. 1997 Dec;69(6):2564-70.


In addition, when complex I and IV activities were titrated with specific inhibitors, thresholds in ATP synthesis and oxygen respiration became apparent.
3(0,0,0,3) Details
215122 Ragan CI, Heron C: The interaction between mitochondrial NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase. Circ Res. 2004 Mar 5;94(4):478-86. Epub 2003 Dec 29.

The NADH-ubiquinone oxidoreductase complex (Complex I) and the ubiquinol-cytochrome c oxidoreductase complex (Complex III) combine in a 1:1 molar ratio to give NADH-cytochrome c oxidoreductase (Complex I-Complex III). 2.
Experiments on the inhibition of the NADH-cytochrome c oxidoreductase activity of mixtures of Complexes I and III by rotenone and antimycin indicate that electron transfer between a unit of Complex I-Complex III and extra molecules of Complexes I or III does not contribute to the overall rate of cytochrome c reduction. 3.
3(0,0,0,3) Details
10797558 Lamensdorf I, Eisenhofer G, Harvey-White J, Hayakawa Y, Kirk K, Kopin IJ: Metabolic stress in PC12 cells induces the formation of the endogenous dopaminergic neurotoxin, 3,4-dihydroxyphenylacetaldehyde. Arch Biochem Biophys. 1995 Jan 10;316(1):70-6.


Using inhibitors of mitochondrial complexes I, II, III and IV we found that inhibition of complex I and III increased levels of DOPAL and DOPET.
3(0,0,0,3) Details
9230920 Zharova TV, Vinogradov AD: A competitive inhibition of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) by ADP-ribose. Neurotoxicol Teratol. 2004 Nov-Dec;26(6):857-64.

Ki for inhibition of the rotenone-sensitive NADH oxidase in SMP by ADPR does not depend on delta mu H+.
2(0,0,0,2) Details
15151993 Gauthier BR, Brun T, Sarret EJ, Ishihara H, Schaad O, Descombes P, Wollheim CB: Oligonucleotide microarray analysis reveals PDX1 as an essential regulator of mitochondrial metabolism in rat islets. Eur J Biochem. 2001 May;268(10):3075-82.

In parallel there was a 50% reduction in mRNA levels for the mitochondrially encoded nd1 gene, a subunit of the NADH dehydrogenase comprising complex I of the mitochondrial respiratory chain.
Rotenone, an inhibitor of complex I, mimicked this effect.
2(0,0,0,2) Details
8377005 Krueger MJ, Sablin SO, Ramsay R, Singer TP: Reactivation of NADH dehydrogenase (complex I) inhibited by 1-methyl-4-(4'-alkylphenyl) pyridinium analogues: a clue to the nature of the inhibition site. Exp Mol Pathol. 2005 Jun;78(3):228-32. Epub 2005 Feb 17.

MPP+ and its analogues have been shown to block electron transport at or near the same site as two powerful inhibitors of mitochondrial respiration, rotenone and piericidin A.
2(0,0,0,2) Details
15958286 del Arenal IP, Rubio ME, Ramirez J, Rendon JL, Escamilla JE: Cyanide-resistant respiration in Taenia crassiceps metacestode (cysticerci) is explained by the H2O2-producing side-reaction of respiratory complex I with O2. Ukr Biokhim Zh. 2004 Jan-Feb;76(1):56-64.

Mitochondrial respiration with NADH as substrate was partially inhibited by rotenone, cyanide and antimycin in decreasing order of effectiveness.
2(0,0,0,2) Details
19495971 Ullrich C, Humpel C: Rotenone Induces Cell Death of Cholinergic Neurons in an Organotypic Co-Culture Brain Slice Model. Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L809-19. Epub 2007 Jun 29.

In summary, inhibition of complex I of the electron transport chain may play a role in neurodegeneration of cholinergic neurons.
1(0,0,0,1) Details
1763894 Larsson NG, Andersen O, Holme E, Oldfors A, Wahlstrom J: Leber's hereditary optic neuropathy and complex I deficiency in muscle. . J Cell Sci. 2007 Mar 1;120(Pt 5):838-48. Epub 2007 Feb 13.

This study showed that there is decreased activity of complex I of the respiratory chain in muscle and that cerebral striatal lesions occur in Leber's hereditary optic neuropathy with the NADH-dehydrogenase 4 gene point mutation.
There was no decrease in complex I activity measured as NADH ferricyanide reductase or rotenone-sensitive NADH cytochrome c reductase activities.
1(0,0,0,1) Details
17954696 Matsumoto J, Sakamoto K, Shinjyo N, Kido Y, Yamamoto N, Yagi K, Miyoshi H, Nonaka N, Katakura K, Kita K, Oku Y: Anaerobic NADH-fumarate reductase system is predominant in the respiratory chain of Echinococcus multilocularis, providing a novel target for the chemotherapy of alveolar echinococcosis. Physiol Plant. 2001 Apr;111(4):448-456.


Furthermore, in vitro treatment assays using respiratory chain inhibitors against the NADH-quinone reductase activity of mitochondrial complex I demonstrated that they had a potent ability to kill protoscoleces.
1(0,0,0,1) Details
17877636 Ma TC, Mihm MJ, Bauer JA, Hoyt KR: Bioenergetic and oxidative effects of free 3-nitrotyrosine in culture: selective vulnerability of dopaminergic neurons and increased sensitivity of non-dopaminergic neurons to dopamine oxidation. Nucl Med Biol. 2007 Jan;34(1):109-16. Epub 2006 Nov 28.

Free 3NT alone directly inhibited mitochondrial complex I, decreased ATP, sensitized neurons to mitochondrial depolarization, and increased superoxide production.
Subtoxic concentrations of rotenone (instead of free 3NT) caused similar results.
1(0,0,0,1) Details
10951577 Chandel NS, Vander Heiden MG, Thompson CB, Schumacker PT: Redox regulation of p53 during hypoxia. . J Bioenerg Biomembr. 2008 Aug;40(4):289-96. Epub 2008 Sep 2.

Rotenone, an inhibitor of mitochondrial complex I, and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, a mitochondrial anion channel inhibitor, also abolished the increase in ROS signal and p53 levels during hypoxia.
Rotenone, an inhibitor of mitochondrial complex I, and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, a mitochondrial anion channel inhibitor, also abolished the increase in ROS signal and p53 levels during hypoxia.
1(0,0,0,1) Details
12473378 Zhou G, Jiang W, Zhao Y, Ma G, Xin W, Yin J, Zhao B: Sodium tanshinone IIA sulfonate mediates electron transfer reaction in rat heart mitochondria. Brain Res. 1997 Nov 28;777(1-2):110-8.

It was found that STS could stimulate mitochondrial NADH oxidation dose-dependently and partly restore NADH oxidation in the presence of respiratory inhibitor (rotenone or antimycin A or KCN).
It was likely that STS could accept electrons from complex I similar to ferricyanide and could be converted to its semiquinone form that could then reduce oxygen molecule.
1(0,0,0,1) Details
6451185 Rouslin W, Millard RW: Mitochondrial inner membrane enzyme defects in porcine myocardial ischemia. J Neurosci Res. 2006 Nov 1;84(6):1376-84.

After 2 h of occlusion, mitochondria from the ischemic area exhibited a 36 +/- 6% drop in state 3 respiratory activity (QO2) supported by the NAD-linked substrates, glutamate plus malate, but only a 5 +/- 3% decrease in QO2 with succinate plus rotenone.
The activity of electron transfer complex I (NADH-CoQ reductase) decreased commensurately by 33 +/- 4% with the decrease in QO2 with NAD-linked substrates.
1(0,0,0,1) Details
508289 Van Hinsbergh VW, Veerkamp JH, Glatz JF: 4-Methyl-2-oxopentanoate oxidation by rat skeletal-muscle mitochondria. . Antimicrob Agents Chemother. 2006 May;50(5):1841-51.

These observations indicate that the branched-chain 2-oxo acid dehydrogenase complex is situated on the inner side of the mitochondrial inner membrane. 6.
Addition of rotenone and simultaneous addition of carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) and valinomycin markedly decreased 4-methyl-2-oxopentanoate oxidation. 5.
1(0,0,0,1) Details
8945906 Goda N, Suematsu M, Mukai M, Kiyokawa K, Natori M, Nozawa S, Ishimura Y: Modulation of mitochondrion-mediated oxidative stress by nitric oxide in human placental trophoblastic cells. Oncogene. 1998 Nov 12;17(19):2515-24.

This oxidative process was completely blocked by rotenone, a reagent that interferes with electron entry into complex I of the mitochondrial respiratory chain.
81(1,1,1,1) Details
17504811 Guidarelli A, Cerioni L, Cantoni O: Inhibition of complex III promotes loss of Ca2+ dependence for mitochondrial superoxide formation and permeability transition evoked by peroxynitrite. Brain Res. 2008 Dec 3;1243:167-73. Epub 2008 Sep 30.

Here we show that formation of H2O2 and DNA damage are suppressed by inhibition of complex I (by rotenone) or ubisemiquinone formation (by myxothiazol), as well as by a variety of manipulations preventing either the mobilization of Ca2+ or its mitochondrial accumulation.
81(1,1,1,1) Details
12832841 Kitamura Y, Inden M, Sanada H, Takata K, Taniguchi T, Shimohama S, Orii H, Mochii M, Agata K, Watanabe K: Inhibitory effects of antiparkinsonian drugs and caspase inhibitors in a parkinsonian flatworm model. Exp Neurol. 2004 Jan;185(1):169-81.

It has been known that rotenone and 1-methyl-4-phenylpyridinium ion (MPP (+), a metabolite of MPTP), which inhibit mitochondrial complex I, are useful tools for parkinsonian models in vertebrates such as primates and rodents.
81(1,1,1,1) Details
18437094 Riess ML, Camara AK, Heinen A, Eells JT, Henry MM, Stowe DF: KATP channel openers have opposite effects on mitochondrial respiration under different energetic conditions. Ukr Biokhim Zh. 2003 Sep-Oct;75(5):69-76.

Oxygen consumption was measured for complex I (pyruvate/malate) or complex II (succinate with rotenone) substrates in mitochondria from fresh guinea pig hearts.
81(1,1,1,1) Details
12171069 Magnitsky S, Toulokhonova L, Yano T, Sled VD, Hagerhall C, Grivennikova VG, Burbaev DS, Vinogradov AD, Ohnishi T: EPR characterization of ubisemiquinones and iron-sulfur cluster N2, central components of the energy coupling in the NADH-ubiquinone oxidoreductase (complex I) in situ. Am J Physiol Renal Physiol. 2004 Apr;286(4):F749-59. Epub 2003 Dec 9.

In the current study, special attention was placed on the SQNf, because of its high sensitivities to DeltamicroH+ and to specific complex I inhibitors (rotenone and piericidin A) in a unique manner.
35(0,1,1,5) Details
18781777 Ichimaru N, Murai M, Kakutani N, Kako J, Ishihara A, Nakagawa Y, Nishioka T, Yagi T, Miyoshi H: Synthesis and characterization of new piperazine-type inhibitors for mitochondrial NADH-ubiquinone oxidoreductase (complex I). Biofactors. 1998;8(3-4):195-204.

The mode of action of Deltalac-acetogenins, strong inhibitors of bovine heart mitochondrial complex I, is different from that of traditional inhibitors such as rotenone and piericidin A [Murai, M., et al. (2007) Biochemistry 46 , 6409-6416].
35(0,1,1,5) Details
12057837 Zhang X, Jones D, Gonzalez-Lima F: Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction. Free Radic Biol Med. 2009 May 1;46(9):1283-97. Epub 2009 Feb 23.

We developed a mouse model of optic neuropathy caused by mitochondrial complex I dysfunction by intravitreal administration of rotenone, a complex I inhibitor, in CBA/J mice.
33(0,1,1,3) Details
18812510 Choi WS, Kruse SE, Palmiter RD, Xia Z: Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat. J Pharmacol Exp Ther. 1998 Mar;284(3):1112-21.

These data suggest that dopaminergic neuron death induced by treatment with rotenone, MPP (+), or paraquat is independent of complex I inhibition.
33(0,1,1,3) Details
18703762 Audi SH, Merker MP, Krenz GS, Ahuja T, Roerig DL, Bongard RD: Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia. Brain Res. 1997 Nov 28;777(1-2):202-9.

In normoxic lungs, CoQ (1) H (2) efflux rates when CoQ (1) was infused decreased by 58 and 33% in the presence of rotenone (mitochondrial complex I inhibitor) and dicumarol [NAD (P) H-quinone oxidoreductase 1 (NQO1) inhibitor], respectively.
33(0,1,1,3) Details
15505787 Valentino ML, Barboni P, Ghelli A, Bucchi L, Rengo C, Achilli A, Torroni A, Lugaresi A, Lodi R, Barbiroli B, Dotti M, Federico A, Baruzzi A, Carelli V: The ND1 gene of complex I is a mutational hot spot for Leber's hereditary optic neuropathy. Am J Physiol Renal Physiol. 2007 Sep;293(3):F723-31. Epub 2007 Jun 27.

Biochemical investigations in platelets showed partially insensitive complex I to rotenone inhibition.
32(0,1,1,2) Details
15905875 Ladha JS, Tripathy MK, Mitra D: Mitochondrial complex I activity is impaired during HIV-1-induced T-cell apoptosis. FEBS Lett. 1997 Jul 28;412(2):265-9.

Finally, sensitivity to complex I inhibitor Rotenone is reduced in HIV-1-infected T cells indicating an important role for it in the death process.
32(0,1,1,2) Details
19009337 Wen JJ, Garg NJ: Mitochondrial generation of reactive oxygen species is enhanced at the Q (o) site of the complex III in the myocardium of Trypanosoma cruzi-infected mice: beneficial effects of an antioxidant. Antioxid Redox Signal. 1999 Spring;1(1):97-104.

Inhibition studies with normal cardiac mitochondria showed that rotenone induced ROS generation at the Q (Nf)-ubisemiquinone site in complex I.
32(0,1,1,2) Details
19633536 Li Y, Rory Goodwin C, Sang Y, Rosen EM, Laterra J, Xia S: Camptothecin and Fas receptor agonists synergistically induce medulloblastoma cell death: ROS-dependent mechanisms. Eur J Cell Biol. 2004 Mar;83(2):51-4.

Moreover, the mitochondrial respiratory chain complex I inhibitor rotenone potentiated CH-11-induced apoptosis in DAOY cells.
31(0,1,1,1) Details
15146976 Bocklinger K, Tomaselli B, Heftberger V, Podhraski V, Bandtlow C, Baier-Bitterlich G: Purine nucleosides support the neurite outgrowth of primary rat cerebellar granule cells after hypoxia. Rev Esp Geriatr Gerontol. 2009 Jul-Aug;44(4):194-9. Epub 2009 Jul 3.

Rotenone, a mitochondrial complex I inhibitor, induced a 30.4 +/- 3.6% loss of viable cells and a 35.0 +/- 4.4% loss of neurite formation of cerebellar granule cells, which was partially restored by the addition of purine nucleosides adenosine, inosine and guanosine.
31(0,1,1,1) Details
7994564 Chen CL, Sangiah S, Yu CA, Chen H, Berlin KD, Garrison GL, Scherlag BJ, Lazzara R: Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca (2+)-ATPase. Res Commun Mol Pathol Pharmacol. 1994 Aug;85(2):193-208.


The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc.
0(0,0,0,0) Details
18471434 Lombardi A, Grasso P, Moreno M, de Lange P, Silvestri E, Lanni A, Goglia F: Interrelated influence of superoxides and free fatty acids over mitochondrial uncoupling in skeletal muscle. Eukaryot Cell. 2006 Sep;5(9):1460-7.


In the absence of FFAs, no differences in proton-leak kinetic were detected between succinate-energized mitochondria respiring in the absence or presence of rotenone, despite a large difference in complex I superoxide production.
0(0,0,0,0) Details
11989755 Bottje W, Iqbal M, Tang ZX, Cawthon D, Okimoto R, Wing T, Cooper M: Association of mitochondrial function with feed efficiency within a single genetic line of male broilers. Poult Sci. 2002 Apr;81(4):546-55.


Electron leak increased following inhibition of electron transport at Complex I (with rotenone) and Complex III (with antimycin A) in low FE but not in high FE breast mitochondria.
0(0,0,0,0) Details
12376345 Schroedl C, McClintock DS, Budinger GR, Chandel NS: Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Mol Cell Biochem. 2008 Jul;314(1-2):45-50. Epub 2008 Apr 15.


Primary evidence for this model comes from the observation that cells treated with complex I inhibitors, such as rotenone, or cells that lack mitochondrial DNA (rho (0)-cells) fail to generate reactive oxygen species or stabilize HIF-1alpha protein in response to hypoxia.
0(0,0,0,0) Details
18224432 Shiryaeva A, Baidyuk E, Arkadieva A, Okovityy S, Morozov V, Sakuta G: Hepatocyte mitochondrion electron-transport chain alterations in CCl (4) and alcohol induced hepatitis in rats and their correction with simvastatin. Biochim Biophys Acta. 2006 May-Jun;1757(5-6):553-61. Epub 2006 Apr 17.

The presented data lead to the assumption that the increased oxygen consumption by the respiratory chain of pathological mitochondria to be linked mainly with the altered function of complex I.
Rotenone resulted in 27% suppression of respiration by pathological hepatocytes whereas 2,4-dinitrophenol produced a 1.4-fold increase of respiration.
1(0,0,0,1) Details
12958040 Cowan DB, Jones M, Garcia LM, Noria S, del Nido PJ, McGowan FX Jr: Hypoxia and stretch regulate intercellular communication in vascular smooth muscle cells through reactive oxygen species formation. J Neurosci Res. 2008 Aug 1;86(10):2339-52.


Using a fluorogenic substrate, hypoxic VSMCs showed increased reactive oxygen species generation, which could be prevented by the glutathione peroxidase mimic ebselen and the mitochondrial complex I inhibitor rotenone but not with the redox-sensitive thiol pyrrolidine dithiocarbamate.
0(0,0,0,0) Details
15694918 Kotake Y, Taguchi R, Okuda K, Sekiya Y, Tasaki Y, Hirobe M, Ohta S: Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins. J Biol Chem. 2003 Sep 19;278(38):36027-31. Epub 2003 Jul 2.


In this study, we examined the neuroprotective effect of 1MeTIQ against four dopaminergic neurotoxins, 1-methyl-4-phenylpyridinuim ion, 6-hydroxydopamine, rotenone, and l-benzyl-1,2,3,4-tetrahydroisoquinoline, in cultured rat mesencephalic neurons. 1MeTIQ exerted neuroprotective action against all these toxins.
0(0,0,0,0) Details
9396723 Guidarelli A, Clementi E, Brambilla L, Cantoni O: Mechanism of the antimycin A-mediated enhancement of t-butylhydroperoxide-induced single-strand breakage in DNA. Chem Biol Interact. 2004 Dec 7;150(3):253-70.


The hypothesis that these effects are selectively linked to inhibition of the electron transport from cytochrome b to cytochrome c1 is validated by the following observations: (1) two complex III inhibitors, antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide, enhanced the tB-OOH-induced DNA cleavage over the same concentration range as that in which inhibition of oxygen consumption was observed; (2) the complex III inhibitor-mediated enhancement of tB-OOH-induced DNA damage was abolished by the complex I inhibitor rotenone or by glucose omission, and (3) the enhancing effects of antimycin A were not observed in respiration-deficient cells.
0(0,0,0,0) Details
17343987 Alvira D, Tajes M, Verdaguer E, de Arriba SG, Allgaier C, Matute C, Trullas R, Jimenez A, Pallas M, Camins A: Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons. J Bioenerg Biomembr. 2008 Feb;40(1):27-34. Epub 2008 Jan 26.


Mitochondrial dysfunction, specifically alteration of the mitochondrial complex I, is the primary target of the parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) induced apoptosis in neurons.
1(0,0,0,1) Details
3134033 Filser M, Werner S: Pethidine analogues, a novel class of potent inhibitors of mitochondrial NADH: ubiquinone reductase. J Neurochem. 2005 Feb;92(4):840-9.

Dose-response curves revealed that the potency of these compounds is very comparable to that of the standard probe rotenone.
The potential advantages of the pethidine derivatives for the investigation of structure - function relationships within complex I of the respiratory chain is discussed.
1(0,0,0,1) Details
17900761 Larsen TR, Soderling AS, Caidahl K, Roepstorff P, Gramsbergen JB: Nitration of soluble proteins in organotypic culture models of Parkinson's disease. J Neurosci. 2002 Aug 15;22(16):7006-15.


Here we quantified protein-bound 3-nitrotyrosine (3-NT) by a novel gas chromatography/negative chemical ionization tandem mass spectrometry technique and DA and 3,4-dihydroxyphenylalanine (DOPA) by HPLC in tissues or medium of organotypic, mouse mesencephalon cultures after acute or chronic treatments with the peroxynitrite donor 3-morpholino-sydnonimine (SIN-1), the dopaminergic toxin 1-methyl-4-phenylpyridinium (MPP (+)) or the lipophilic complex I inhibitor rotenone.
0(0,0,0,0) Details
17596522 Zhang A, Jia Z, Guo X, Yang T: Aldosterone induces epithelial-mesenchymal transition via ROS of mitochondrial origin. Biochim Biophys Acta. 2007 Jul;1767(7):940-7. Epub 2007 Apr 6.


Aldo-induced oxidative stress and EMT were both abolished by the mitochondrial respiratory chain complex I inhibitor rotenone, but not the NADPH oxidase inhibitor apocynin.
0(0,0,0,0) Details
6317378 Demant EJ: NADH oxidation in submitochondrial particles protects respiratory chain activity against damage by adriamycin-Fe3+. Neurotoxicology. 2009 Jul;30(4):589-98. Epub 2009 Apr 1.

Protection by NADH is strengthened by removal of cytochrome c from the submitochondrial particles and by antimycin A but abolished by rotenone.
Inhibition of cytochrome c oxidase activity by the adriamycin-Fe3+ complex is reversible and activity is recovered upon cholate solubilization of the particles.
1(0,0,0,1) Details
16243845 Panov A, Dikalov S, Shalbuyeva N, Taylor G, Sherer T, Greenamyre JT: Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication. Nucl Med Biol. 1995 May;22(4):491-6.

In Rot rat brain mitochondria (Rot-RBM) there was a 30-40% inhibition of respiration in State 3 and State 3U with Complex I (Co-I) substrates and succinate.
1(0,0,0,1) Details
19409963 Caudle WM, Kitsou E, Li J, Bradner J, Zhang J: A role for a novel protein, nucleolin, in Parkinson's disease. FEBS Lett. 2007 Dec 22;581(30):5803-6. Epub 2007 Nov 26.


Furthermore, manipulation of nucleolin in an in vitro model of PD resulted in significant alterations in the generation of oxidative stress as well as proteasomal inhibition following rotenone exposure.
0(0,0,0,0) Details
2846570 Krishnamoorthy G, Hinkle PC: Studies on the electron transfer pathway, topography of iron-sulfur centers, and site of coupling in NADH-Q oxidoreductase. Biochem J. 1996 Aug 15;318 ( Pt 1):343-9.


N-Bromosuccinimide also destroyed the signal from N-4 but without inhibiting rotenone-sensitive electron transfer to quinone, suggesting a branched pathway for electron transfer.
0(0,0,0,0) Details
15317809 Muller FL, Liu Y, Van Remmen H: Complex III releases superoxide to both sides of the inner mitochondrial membrane. Biochem J. 1977 Jun 1;163(3):605-15.


This finding fits well with the proposed site of electron leak at Complex I, namely the iron-sulfur clusters of the (matrix-protruding) hydrophilic arm.
1(0,0,0,1) Details
20056551 Mou T, Jing H, Yang W, Fang W, Peng C, Guo F, Zhang X, Pang Y, Ma Y: Preparation and biodistribution of [18F] FP2OP as myocardial perfusion imaging agent for positron emission tomography. J Biol Chem. 2004 Nov 19;279(47):49064-73. Epub 2004 Aug 17.

Ex vivo autoradiography demonstrates that [(18) F] FP2OP may have high affinity with MC-I and that can be blocked by [(19) F] FP2OP or rotenone (a known MC-I inhibitor).
Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow.
1(0,0,0,1) Details
18786503 Lin SS, Kerscher S, Saleh A, Brandt U, Gross U, Bohne W: The Toxoplasma gondii type-II NADH dehydrogenase TgNDH2-I is inhibited by 1-hydroxy-2-alkyl-4 (1H) quinolones. Basic Res Cardiol. 2003 Mar;98(2):114-23.


The apicomplexan parasite Toxoplasma gondii does not possess complex I of the mitochondrial respiratory chain, but has two genes encoding rotenone-insensitive, non-proton pumping type-II NADH dehydrogenases (NDH2s).
0(0,0,0,0) Details
20227863 He M, Siow RC, Sugden D, Gao L, Cheng X, Mann GE: Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: A role for Nrf2 in vascular protection in diabetes. FEBS Lett. 1994 Oct 3;352(3):375-9.


Inhibition of ROS production with the superoxide scavenger Tiron or inhibitors of flavoproteins (diphenylene iodonium) and NADPH oxidase (apocynin), but not eNOS (l-NAME) or mitochondria complex I (rotenone) abrogated HO-1 induction by AGE-BSA.
0(0,0,0,0) Details
11798036 Leverve XM, Fontaine E: Role of substrates in the regulation of mitochondrial function in situ. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1275-9.


We then review results indicating that the activity of complex I directly regulates the PTP, a finding that emphasizes the importance of the respiratory substrates in PTP regulation.
1(0,0,0,1) Details
9878531 Li Y, Trush MA: Diphenyleneiodonium, an NAD (P) H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production. J Bioenerg Biomembr. 2001 Jun;33(3):251-7.

DPI was as potent as rotenone in inhibiting the production of superoxide and H2O2 by mitochondrial respiration.
With substrate-supported isolated mitochondria, DPI was shown to reduce mitochondrial superoxide production probably through inhibiting NADH-ubiquinone oxidoreductase (complex I).
1(0,0,0,1) Details
15843045 Tomaselli B, Podhraski V, Heftberger V, Bock G, Baier-Bitterlich G: Purine nucleoside-mediated protection of chemical hypoxia-induced neuronal injuries involves p42/44 MAPK activation. Oncogene. 2005 May 26;24(23):3715-25.

O (2)-sensitive neuronal pheochromocytoma (PC12)-cells, which are widely used as a model system for sympathetic ganglion-like neurons, were subjected to chemical hypoxia induced with rotenone, an inhibitor of mitochondrial complex I.
O (2)-sensitive neuronal pheochromocytoma (PC12)-cells, which are widely used as a model system for sympathetic ganglion-like neurons, were subjected to chemical hypoxia induced with rotenone, an inhibitor of mitochondrial complex I.
1(0,0,0,1) Details
8522981 Budd SL, Nicholls DG: A reevaluation of the role of mitochondria in neuronal Ca2+ homeostasis. Antioxid Redox Signal. 1999 Fall;1(3):285-95.


The further addition of the mitochondrial complex I inhibitor rotenone led to a collapse of the mitochondrial membrane potential, monitored by rhodamine-123, but had no effect on ATP/ADP ratios.
0(0,0,0,0) Details
16154284 Campanucci VA, Brown ST, Hudasek K, O'kelly IM, Nurse CA, Fearon IM: O2 sensing by recombinant TWIK-related halothane-inhibitable K+ channel-1 background K+ channels heterologously expressed in human embryonic kidney cells. Chem Res Toxicol. 2004 Nov;17(11):1540-8.


Neither the mitochondrial complex I inhibitors rotenone, myxothiazol and sodium cyanide, nor the NADPH oxidase inhibitors diphenylene iodonium and phenylarsine oxide, were effective in inhibiting the O2-sensitivity of THIK-1.
0(0,0,0,0) Details
15650392 Bundy RE, Hoare GS, Kite A, Beach J, Yacoub M, Marczin N: Redox regulation of p38 MAPK activation and expression of ICAM-1 and heme oxygenase-1 in human alveolar epithelial (A549) cells. Anal Chem. 2006 Apr 1;78(7):2422-31.


The mitochondrial complex I and III inhibitors, rotenone and antimycin A, and allopurinol partially inhibited H2O2- but not TNFalpha-induced p38 activation.
0(0,0,0,0) Details
19488053 Torres S, Salgado-Ceballos H, Guizar-Sahagun G, Torres JL, Orozco-Suarez S, Diaz-Ruiz A, Vazquez ME, Collado C, Rios C: Deleterious versus neuroprotective effect of metabolic inhibition after traumatic spinal cord injury. Spinal Cord. 2009 Oct;47(10):745-50. Epub 2009 Jun 2.


METHODS: Animals were divided into five groups: one sham and four with TSCI, including no treatment, rotenone (inhibitor of mitochondrial complex I), sodium azide (inhibitor of mitochondrial complex IV) and pyrophosphate of thiamine or non-degradable cocarboxylase as a metabolic reactivator.
0(0,0,0,0) Details
18234847 Buttigieg J, Brown ST, Lowe M, Zhang M, Nurse CA: Functional mitochondria are required for O2 but not CO2 sensing in immortalized adrenomedullary chromaffin cells. Mech Ageing Dev. 2005 Apr;126(4):505-11. Epub 2004 Dec 15.


Rotenone (1 microM), a mitochondrial complex I blocker known to mimic and occlude the effects of hypoxia in primary AMC, was effective in wild-type but not rho (0) MAH cells.
0(0,0,0,0) Details
14732287 Herrera B, Murillo MM, Alvarez-Barrientos A, Beltran J, Fernandez M, Fabregat I: Source of early reactive oxygen species in the apoptosis induced by transforming growth factor-beta in fetal rat hepatocytes. J Neurochem. 2008 Apr;105(2):360-8. Epub 2007 Nov 25.


Rotenone, an inhibitor of the NADH dehydrogenase in mitochondrial complex I, attenuated, but did not completely inhibit, ROS-production, caspase activation, and cell death mediated by TGF-beta.
0(0,0,0,0) Details
17069748 Belyaeva EA, Dymkowska D, Wieckowski MR, Wojtczak L: Reactive oxygen species produced by the mitochondrial respiratory chain are involved in Cd2+-induced injury of rat ascites hepatoma AS-30D cells. Neuroscience. 2009 Oct 20;163(3):735-40. Epub 2009 Jul 4.


Inhibitors of the mitochondrial permeability transition pore, cyclosporin A and bongkrekic acid, and inhibitors of respiratory complex III, stigmatellin and antimycin A, but not inhibitor of complex I, rotenone, partly prevented necrosis evoked by exposure of the cells to Cd (2+).
0(0,0,0,0) Details
11370674 Velazquez I, Pardo JP: Kinetic characterization of the rotenone-insensitive internal NADH: ubiquinone oxidoreductase of mitochondria from Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1998 Dec 18;253(2):295-9.

Due to the fact that S. cerevisiae cells lack complex I, the expression of this protein is essential for cell growth under respiratory conditions.
1(0,0,0,1) Details
12226375 Moller IM, Roberts TH, Rasmusson AG: Ubiquinone-1 Induces External Deamino-NADH Oxidation in Potato Tuber Mitochondria. Plant Physiol. 1996 Sep;112(1):75-78.


We conclude that UQ-1-induced external deamino-NADH oxidation is due to a change in specificity of the external rotenone-insensitive NADH dehydrogenase.
0(0,0,0,0) Details
7767529 Hokanson JF, Mercier JG, Brooks GA: Cyclosporine A decreases rat skeletal muscle mitochondrial respiration in vitro. J Bioenerg Biomembr. 1998 Jun;30(3):235-43.


CsA inhibited maximal respiration (ADP stimulated) in the presence of succinate and rotenone by 18.3% and in the presence of malate and pyruvate by 34.7%.
0(0,0,0,0) Details
7476912 Garcia-Ruiz C, Colell A, Morales A, Kaplowitz N, Fernandez-Checa JC: Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes. J Plant Physiol. 2006 Jul;163(8):877-82. Epub 2005 Nov 9.


However, blockade of complex I or II with rotenone or thenoyltrifluoroacetone, respectively, did not result in accumulation of hydrogen peroxide.
0(0,0,0,0) Details
8505638 Anderson JJ, Bravi D, Ferrari R, Davis TL, Baronti F, Chase TN, Dagani F: No evidence for altered muscle mitochondrial function in Parkinson's disease. Mol Biochem Parasitol. 1984 Oct;13(2):121-34.


Likewise, activities of rotenone sensitive NADH cytochrome c reductase, succinate cytochrome c reductase, or cytochrome oxidase in muscle mitochondria were not significantly different between Parkinsonian and control subjects.
0(0,0,0,0) Details
12091466 Gluck M, Ehrhart J, Jayatilleke E, Zeevalk GD: Inhibition of brain mitochondrial respiration by dopamine: involvement of H (2) O (2) and hydroxyl radicals but not glutathione-protein-mixed disulfides. Am J Physiol Cell Physiol. 2007 Jul;293(1):C22-9. Epub 2007 Apr 11.


Co-administration of desferrioxamine with H (2) O (2) had no effect on complex I-associated inhibition in intact mitochondria, but attenuated inhibition of rotenone-sensitive NADH oxidase activity by 70% in freeze-thawed mitochondria.
0(0,0,0,0) Details
20035277 Wang T, Si Y, Shirihai OS, Si H, Schultz V, Corkey RF, Hu L, Deeney JT, Guo W, Corkey BE: Respiration in Adipocytes is Inhibited by Reactive Oxygen Species. Obesity (Silver Spring). 2009 Dec 24.


Importantly, the ROS scavenging role of pyruvate was not affected by rotenone, an inhibitor of mitochondrial complex I.
0(0,0,0,0) Details
15356189 Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS, Beal MF: Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. Brain Res. 2009 Jul 7;1279:1-8. Epub 2009 May 13.


In the absence of ADP or in the presence of rotenone, H (2) O (2) production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of alpha-ketoglutarate.
0(0,0,0,0) Details
16251452 Bao L, Avshalumov MV, Rice ME: Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion. Biochim Biophys Acta. 2003 Dec 8;1607(2-3):79-90.


We show here that acute exposure to the mitochondrial complex I inhibitor rotenone (30-100 nM; 30 min) causes concentration-dependent suppression of single-pulse evoked dopamine (DA) release monitored in real time with carbon-fiber microelectrodes in guinea pig striatal slices, with no effect on DA content.
0(0,0,0,0) Details
19028798 Yamaguchi O, Kaneshiro T, Saitoh S, Ishibashi T, Maruyama Y, Takeishi Y: Regulation of coronary vascular tone via redox modulation in the alpha1-adrenergic-angiotensin-endothelin axis of the myocardium. J Immunol Methods. 2007 Sep 30;326(1-2):76-82. Epub 2007 Aug 1.


Dihydroethidium (DHE) and dichlorodihydrofluorescein (DCF) intensities were increased by phenylephrine stimulation in isolated rat cardiac myocytes, which were enhanced by the mitochondrial electron transport chain complex I inhibitor rotenone (DHE: 20.4 +/- 1.2-fold and DCF: 25.2 +/- 0.9-fold, n = 8, P < 0.01, respectively) but not by the NADPH oxidase inhibitor apocynin.
0(0,0,0,0) Details
7763312 Anderson WM, Trgovcich-Zacok D: Carbocyanine dyes with long alkyl side-chains: broad spectrum inhibitors of mitochondrial electron transport chain activity. J Neurochem. 2003 Jan;84(1):112-8.


Certain indocarbocyanine, thiacarbocyanine, and oxacarbocyanine dyes possessing short alkyl side-chains (one to five carbons) are potent inhibitors of mammalian mitochondrial NADH-ubiquinone reductase (EC 1.6.99.3) activity (Anderson et al., Biochem Pharmacol 41: 677-684, 1991; Anderson et al., Biochem Pharmacol 45: 691-696, 1993; Anderson et al., Biochem Pharmacol 45: 2115-2122, 1993), and act similarly to rotenone.
0(0,0,0,0) Details
18945820 Shin SM, Kim SG: Inhibition of arachidonic acid and iron-induced mitochondrial dysfunction and apoptosis by oltipraz and novel 1,2-dithiole-3-thione congeners. Nature. 1995 Oct 5;377(6548):438-41.


Oltipraz was found to attenuate apoptosis induced by rotenone (complex I inhibitor), but not that by antimycin A (complex III inhibitor), suggesting that the inhibition of AA-induced apoptosis by oltipraz might be associated with the electron transport system.
0(0,0,0,0) Details
11569921 Ishiguro H, Yasuda K, Ishii N, Ihara K, Ohkubo T, Hiyoshi M, Ono K, Senoo-Matsuda N, Shinohara O, Yosshii F, Murakami M, Hartman PS, Tsuda M: Enhancement of oxidative damage to cultured cells and Caenorhabditis elegans by mitochondrial electron transport inhibitors. Mol Pharmacol. 2009 Jan;75(1):242-53. Epub 2008 Oct 22.


Oxygen loading enhanced the damage of PC 12 cells by thenoyltrifluoroacetone (TTFA, a complex II inhibitor), but did not by rotenone (a complex I inhibitor), antimycin (a complex III inhibitor), and sodium azide (a complex IV inhibitor).
0(0,0,0,0) Details
4315616 Gutman M, Singer TP, Beinert H, Casida JE: Reaction sites of rotenone, piericidin A, and amytal in relation to the nonheme iron components of NADH dehydrogenase. J Neurochem. 2008 Jul;106(2):826-34. Epub 2008 Apr 28.

0(0,0,0,0) Details
12401552 Kitamura Y, Inden M, Miyamura A, Kakimura J, Taniguchi T, Shimohama S: Possible involvement of both mitochondria- and endoplasmic reticulum-dependent caspase pathways in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. Chem Res Toxicol. 2004 Sep;17(9):1272-9.

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8944779 Beattie DS, Howton MM: The presence of rotenone-sensitive NADH dehydrogenase in the long slender bloodstream and the procyclic forms of Trypanosoma brucei brucei. Biochemistry. 2009 Mar 10;48(9):2053-62.

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12270629 Fang J, Beattie DS: Rotenone-insensitive NADH dehydrogenase is a potential source of superoxide in procyclic Trypanosoma brucei mitochondria. FEBS J. 2007 Jun;274(12):3150-8. Epub 2007 May 22.

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8442768 Anderson WM, Delinck DL, Benninger L, Wood JM, Smiley ST, Chen LB: Cytotoxic effect of thiacarbocyanine dyes on human colon carcinoma cells and inhibition of bovine heart mitochondrial NADH-ubiquinone reductase activity via a rotenone-type mechanism by two of the dyes. Biochim Biophys Acta. 2002 Oct 3;1556(1):73-80.

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15140267 Geisler DA, Johansson FI, Svensson AS, Rasmusson AG: Antimycin A treatment decreases respiratory internal rotenone-insensitive NADH oxidation capacity in potato leaves. Biochim Biophys Acta. 1998 May 6;1364(2):222-35.

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11597127 Guidarelli A, Clementi E, De Nadai C, Bersacchi R, Cantoni O: TNFalpha enhances the DNA single-strand breakage induced by the short-chain lipid hydroperoxide analogue tert-butylhydroperoxide via ceramide-dependent inhibition of complex III followed by enforced superoxide and hydrogen peroxide formation. Mitochondrion. 2006 Oct;6(5):235-44. Epub 2006 Aug 3.


The following lines of evidence suggest that the enhancing effects of TNFalpha are mediated by inhibition of complex III and by the ensuing formation of superoxides and hydrogen peroxide: (a) the effects of TNFalpha were mimicked by the complex III inhibitor antimycin A; (b) the effects of TNFalpha, or antimycin A, were abolished by the complex I inhibitor rotenone, or by myxothiazol, an agent which inhibits the electron flow from the reduced coenzyme Q to cytochrome c (1) and therefore prevents ubisemiquinone formation; (c) the effects of TNFalpha, or antimycin A, were not observed in respiration-deficient cells; and (d) the effects of TNFalpha, or antimycin A, were sensitive to catalase.
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19013527 Meurers BH, Zhu C, Fernagut PO, Richter F, Hsia YC, Fleming SM, Oh M, Elashoff D, Dicarlo CD, Seaman RL, Chesselet MF: Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo. J Bioenerg Biomembr. 2002 Apr;34(2):89-94.

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17951219 Sharifpanah F, Wartenberg M, Hannig M, Piper HM, Sauer H: Peroxisome proliferator-activated receptor alpha agonists enhance cardiomyogenesis of mouse ES cells by utilization of a reactive oxygen species-dependent mechanism. Cancer Res. 1990 Dec 15;50(24):7876-81.


Treatment with PPARalpha, but not PPARbeta, and PPARgamma agonists and MK886, resulted in generation of reactive oxygen species (ROS), which was inhibited in the presence of the NADPH oxidase inhibitors diphenylen iodonium (DPI) and apocynin and the free radical scavengers vitamin E and N-(2-mercapto-propionyl)-glycine (NMPG), whereas the mitochondrial complex I inhibitor rotenone was without effects.
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18646208 Maalouf M, Rho JM: Oxidative impairment of hippocampal long-term potentiation involves activation of protein phosphatase 2A and is prevented by ketone bodies. J Biol Chem. 2004 Nov 12;279(46):47961-7. Epub 2004 Sep 3.


We found that: 1) a combination of ACA and BHB (1 mM each) prevented impairment of LTP by H (2) O (2) (200 microM); 2) KB significantly lowered intracellular levels of reactive oxygen species (ROS)--measured with the fluorescent indicator carboxy-H (2) DCFDA (carboxy-2',7'-dichlorodihydrofluorescein diacetate)--in CA1 pyramidal neurons exposed to H (2) O (2); 3) the effect of KB on LTP was replicated by the protein phosphatase 2A (PP2A) inhibitor fostriecin; 4) KB prevented impairment of LTP by the PP2A activator C (6) ceramide; 5) fostriecin did not prevent the increase in ROS levels in CA1 pyramidal neurons exposed to H (2) O (2), and C (6) ceramide did not increase ROS levels; 6) PP2A activity was enhanced by both H (2) O (2) and rotenone (a mitochondrial complex I inhibitor that increases endogenous superoxide production); and 7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H (2) O (2) or ceramide.
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17018646 Ramachandiran S, Hansen JM, Jones DP, Richardson JR, Miller GW: Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: oxidation of thioredoxin and caspase-3 activation. FEBS Lett. 2003 Aug 14;549(1-3):39-42.

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18487445 Viel EC, Benkirane K, Javeshghani D, Touyz RM, Schiffrin EL: Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats. Clin Chem. 2000 Mar;46(3):345-50.


O (2)(*-) generation decreased with in situ treatment by tenoyltrifluoroacetone and CCCP, inhibitors of mitochondrial electron transport complexes II and IV, respectively, whereas rotenone (mitochondrial complex I inhibitor) had no effect.
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11579170 Leach RM, Hill HM, Snetkov VA, Robertson TP, Ward JP: Divergent roles of glycolysis and the mitochondrial electron transport chain in hypoxic pulmonary vasoconstriction of the rat: identity of the hypoxic sensor. Am J Physiol Regul Integr Comp Physiol. 2010 Apr;298(4):R1026-34. Epub 2010 Jan 20.


Inhibition of complex I of the ETC with rotenone (100 nM) or complex III with myxothiazol (100 nM) did not cause vasoconstriction in normoxia, but abolished both phases of HPV.
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15764673 Bailey SR, Mitra S, Flavahan S, Flavahan NA: Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries. Brain Res Dev Brain Res. 1990 Aug 1;55(1):51-5.


The inhibitor of mitochondrial complex I rotenone (10 micromol/l), the antioxidant N-acetylcysteine (NAC; 20 mmol/l), or the cell-permeable mimic of superoxide dismutase MnTMPyP (50 micromol/l) did not affect vasoconstriction to alpha2-AR stimulation (UK-14304) at 37 degrees C but dramatically inhibited the response at 28 degrees C.
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8226719 Moller IM, Rasmusson AG, Fredlund KM: NAD (P) H-ubiquinone oxidoreductases in plant mitochondria. . J Neurosci. 2008 Dec 10;28(50):13511-21.


On the outer surface, facing the intermembrane space and the cytoplasm, NADH and NADPH are oxidized by what is probably a single low-molecular-weight, nonproton-pumping, unspecific rotenone-insensitive NAD (P) H dehydrogenase.
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12623788 da Silva MM, Sartori A, Belisle E, Kowaltowski AJ: Ischemic preconditioning inhibits mitochondrial respiration, increases H2O2 release, and enhances K+ transport. Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H154-62. Epub 2003 Mar 6.


Preconditioning also increased mitochondrial H2O2 release, an effect related to respiratory inhibition, because it is not observed in the presence of succinate plus rotenone and can be mimicked by chemically inhibiting complex I in the presence of NADH-linked substrates.
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19129916 Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH: Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. J Biol Chem. 2002 Feb 15;277(7):5411-7. Epub 2001 Nov 27.


By in vitro modeling increased mtDNA damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, we found that the phagocytic activity was not altered but that there were: 1) increased autophagic markers, 2) decreased lysosomal activity, 3) increased exocytotic activity and 4) release of chemoattractants.
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16186119 Fujii N, Hirshman MF, Kane EM, Ho RC, Peter LE, Seifert MM, Goodyear LJ: AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle. PLoS One. 2009 Nov 18;4(11):e7878.


Known AMPK stimuli including 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), rotenone (a Complex I inhibitor), dinitrophenol (a mitochondrial uncoupler), muscle contraction, and sorbitol (producing hyperosmolar shock) did not increase AMPK alpha2 activity in alpha2i TG mice, whereas alpha1 activation was attenuated by only 30-50%.
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14699012 Cherednichenko G, Zima AV, Feng W, Schaefer S, Blatter LA, Pessah IN: NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release. Free Radic Biol Med. 2008 Apr 1;44(7):1443-51. Epub 2008 Jan 11.


A significant contribution by mitochondria was excluded as NADH oxidation by SR exhibited > 9-fold higher catalytic activity (8.8 micromol/mg protein per minute) in the absence of exogenous mitochondrial complex I (ubiquinone) or complex III (cytochrome c) electron acceptors, but was inhibited by rotenone and pyridaben (IC50=2 to 3 nmol/L), antimycin A (IC50=13 nmol/L), and diphenyleneiodonium (IC50=28 micromol/L).
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12576057 Gostimskaya IS, Grivennikova VG, Zharova TV, Bakeeva LE, Vinogradov AD: In situ assay of the intramitochondrial enzymes: use of alamethicin for permeabilization of mitochondria. IUBMB Life. 2001 Sep-Nov;52(3-5):221-9.


Alamethicin-treated mitochondria show high rotenone-sensitive NADH oxidase, NADH-quinone reductase, and oligomycin-sensitive and carboxyatractylate-insensitive ATPase activities.
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18456002 Liu F, Hindupur J, Nguyen JL, Ruf KJ, Zhu J, Schieler JL, Bonham CC, Wood KV, Davisson VJ, Rochet JC: Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson's disease-related insults. Free Radic Biol Med. 2008 Aug 1;45(3):242-55. Epub 2008 Apr 11.


Here, we show that MsrA suppresses dopaminergic cell death and protein aggregation induced by the complex I inhibitor rotenone or mutant alpha-synuclein, but not by the proteasome inhibitor MG132.
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7840680 Taylor DE, Ghio AJ, Piantadosi CA: Reactive oxygen species produced by liver mitochondria of rats in sepsis. . Exp Neurol. 2009 May;217(1):231-4. Epub 2009 Jan 29.


Inhibition of electron transport at Complex I with rotenone had no effect on this pattern of OH. production, but rotenone and cyanide abolished the differences in OH. formation between control and septic liver mitochondria.
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11741286 Armstrong JS, Hornung B, Lecane P, Jones DP, Knox SJ: Rotenone-induced G2/M cell cycle arrest and apoptosis in a human B lymphoma cell line PW. Tsitologiia. 2004;46(11):985-92.

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12130563 Hsieh TJ, Zhang SL, Filep JG, Tang SS, Ingelfinger JR, Chan JS: High glucose stimulates angiotensinogen gene expression via reactive oxygen species generation in rat kidney proximal tubular cells. Endocrinology. 2002 Aug;143(8):2975-85.


These effects of high glucose were blocked by antioxidants (taurine and tiron), inhibitors of mitochondrial electron transport chain complex I (rotenone) and II (thenoyltrifluoroacetone), an inhibitor of glycolysis-derived pyruvate transport into mitochondria (alpha-cyano-4-hydroxycinnamic acid), an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone), a manganese superoxide dismutase mimetic, catalase, and a specific inhibitor of p38 MAPK (SB 203580), but were not affected by an inhibitor of the malate-aspartate shuttle (aminooxyacetate acid).
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11239497 Guo Q, Tirosh O, Packer L: Inhibitory effect of alpha-lipoic acid and its positively charged amide analogue on nitric oxide production in RAW 264.7 macrophages. Exp Neurol. 2007 Oct;207(2):218-26. Epub 2007 Jun 29.


Furthermore, in the presence of 2.5 or 25 mM glucose, the inhibitory effects of R (+) LA and R (+) LA-plus on NO production were decreased markedly, while they showed more potent inhibitory effects in the presence of 2 microM rotenone or 5 microg/mL of antimycin A, inhibitors of mitochondrial complex I and complex III, respectively.
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19232048 Tarasenko VI, Garnik EY, Shmakov VN, Konstantinov YM: Induction of Arabidopsis gdh2 gene expression during changes in redox state of the mitochondrial respiratory chain. Biochem J. 1988 Aug 15;254(1):303-5.


Inhibition of complex I by rotenone did not influence the transcript level, but treatment with potassium cyanide, a complex IV inhibitor, also increased the transcript content.
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