Irreversible Inhibition of Mitochondrial Complex I by 1‐Methyl‐4‐Phenylpyridinium: Evidence for Free Radical Involvement
- 1 February 1992
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 58 (2) , 786-789
- https://doi.org/10.1111/j.1471-4159.1992.tb09789.x
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.Keywords
This publication has 27 references indexed in Scilit:
- 1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particlesBiochemical and Biophysical Research Communications, 1990
- Mitochondrial Complex I Deficiency in Parkinson's DiseaseJournal of Neurochemistry, 1990
- Chemically induced parkinson's disease II: Intermediates in the oxidation and reduction reactions of the 1-methyl-4-phenyl-2,3-dihydropyridinium ion and its deprotonated formBiochemical and Biophysical Research Communications, 1989
- Model study on the bioreduction of paraquat, MPP+, and analogs. Evidence against a “redox cycling” mechanism in MPTP neurotoxicityBiochemical and Biophysical Research Communications, 1987
- Chemically induced Parkinson's disease: Intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ionBiochemical and Biophysical Research Communications, 1987
- Formation of superoxide and hydroxyl radicals from 1-methyl-4-phenylpyridinium ion(MPP+): Reductive activation by NADPH cytochrome P-450 reductaseBiochemical and Biophysical Research Communications, 1986
- 1-methyl-4-phenylpyridine (MPP+) induces oxidative stress in the rodentLife Sciences, 1986
- Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity by the antioxidant ascorbic acidNeuropharmacology, 1985
- The specific vulnerability of the substantia nigra to MPTP is related to the presence of transition metalsBiochemical and Biophysical Research Communications, 1985
- Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog SynthesisScience, 1983