Irreversible Inhibition of Mitochondrial Complex I by 1-Methyl-4-Phenylpyridinium: Evidence for Free Radical Involvement
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 58, Issue 2, pages 786–789, February 1992
How to Cite
Cleeter, M. W. J., Cooper, J. M. and Schapira, A. H. V. (1992), Irreversible Inhibition of Mitochondrial Complex I by 1-Methyl-4-Phenylpyridinium: Evidence for Free Radical Involvement. Journal of Neurochemistry, 58: 786–789. doi: 10.1111/j.1471-4159.1992.tb09789.x
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- Received November 8, 1991; accepted November 11, 1991.
- Complex I;
- Free radicals;
- Parkinson's disease
Abstract: Incubation of 10 mM I-methyl-4-phenylpyridinium (MPP+) with sonicated beef heart mitochondria caused an irreversible time-dependent decrease in NADH-ubiquinone-l (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.