N-acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice: implications for treatment of Parkinson's disease.
It has been suggested that thiolic groups are essential for complex I activity and other respiratory mitochondrial enzymes. Recent experiments showed that the thiolic antioxidant N-acetylcysteine (NAC) can protect against age-related decrease in complex I activity in mice hepatic mitochondria. The present paper shows that NAC enhances complex I activity in vitro in synaptic mitochondria isolated from old mice. The optimum NAC concentration for maximum complex I activity was 10 mM in old synaptic preparations. Our data suggest that mitochondrial thiolic groups, which are essentials to oxidative phosphorylation, are impaired by aging. Based on the finding of decreased mitochondrial complex I activity in the substantia nigra of patients with Parkinson's disease, we propose that the thiol-containing antioxidant NAC could be beneficial for treatment of the disease.
Martínez Banaclocha
M
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Department of Pathology, Hospital Universitario La Paz, Madrid, Spain.
D000111:Acetylcysteine / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D042967:Electron Transport Complex I; D016166:Free Radical Scavengers / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects* / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D016166:Free Radical Scavengers; D013438:Sulfhydryl Compounds; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D000111:Acetylcysteine