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IRREVERSIBLE INHIBITION OF MITOCHONDRIAL COMPLEX-I BY 1-METHYL-4-PHENYLPYRIDINIUM - EVIDENCE FOR FREE-RADICAL INVOLVEMENT

CLEETER, MWJ; COOPER, JM; SCHAPIRA, AHV; (1992) IRREVERSIBLE INHIBITION OF MITOCHONDRIAL COMPLEX-I BY 1-METHYL-4-PHENYLPYRIDINIUM - EVIDENCE FOR FREE-RADICAL INVOLVEMENT. J NEUROCHEM , 58 (2) 786 - 789.

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Abstract

Incubation of 10 mM 1-methyl-4-phenylpyridinium (MPP+) with sonicated beef heart mitochondria caused an irreversible time-dependent decrease in NADH-ubiquinone-1 (CoQ1) reductase activity (52% inhibition after 1 h). Inclusion of glutathione, ascorbate, or catalase in the incubation mixture protected the NADH-CoQ1 reductase activity. These results suggest that the interaction of MPP+ with complex I induces free radical generation, which in turn leads to the irreversible inhibition of complex I activity. The generation of free radicals by neurotoxin-induced inhibition of complex I has important implications for our interpretation of the increased oxidative stress observed in Parkinson's disease substantia nigra and for our understanding of the cause(s) of dopaminergic cell death in this disorder.

Type: Article
Title: IRREVERSIBLE INHIBITION OF MITOCHONDRIAL COMPLEX-I BY 1-METHYL-4-PHENYLPYRIDINIUM - EVIDENCE FOR FREE-RADICAL INVOLVEMENT
Keywords: 1-METHYL-4-PHENYLPYRIDINIUM, COMPLEX-I, FREE RADICALS, PARKINSONS DISEASE, INDUCED PARKINSONS-DISEASE, SUBSTANTIA NIGRA, LIPID-PEROXIDATION, NADH DEHYDROGENASE, MPP+, 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE, SUPEROXIDE, DEFICIENCY, MPTP, ION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical Neuroscience
URI: http://discovery.ucl.ac.uk/id/eprint/192493
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