Smoking and mitochondrial function: a model for environmental toxins.
Defects of the human mitochondrial respiratory chain have been associated with several diseases including, most recently, certain neurodegenerative disorders. Several studies have used platelet mitochondrial function as a means to determine the potential contribution of respiratory chain defects to the pathogenesis of Parkinson's disease. Platelet biochemistry is subject to modulation by numerous factors that may circulate in the blood, including environmental agents, some of which may be relevant to mitochondrial dysfunction and neuronal toxicity. We measured mitochondrial respiratory chain enzyme activities in platelets from 18 normal healthy non-smoking controls and compared them with those from 23 similarly healthy cigarette smoking individuals. A 24% decrease (p < 0.02) was observed in the mean NADH CoQ1 reductase (complex I) activity of the smoking group compared with that of the non-smoking group. There was no significant change in the activity of any of the other respiratory chain enzymes. This is the first demonstration in vivo of mitochondrial inhibition by a common environmental agent. The results offer a novel mechanism of action for the cellular toxicity, or even mutagenicity, associated with cigarette smoking. In addition, these data have important implications for the interpretation of platelet mitochondrial complex I activities in disease states. They are particularly relevant to our interpretation and understanding of the complex I deficiency in Parkinson's disease platelets.
Smith
P R
PR
Department of Neurological Science, Royal Free Hospital School of Medicine, London, UK.
Cooper
J M
JM
Govan
G G
GG
Harding
A E
AE
Schapira
A H
AH
D001792:Blood Platelets / Q000201:enzymology; D002950:Citrate (si)-Synthase / Q000097:blood; D004579:Electron Transport; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D012907:Smoking / Q000009:adverse effects*; D013384:Succinate Cytochrome c Oxidoreductase / Q000097:blood
D013384:Succinate Cytochrome c Oxidoreductase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I