Complex I and Parkinson's disease.
Complex I of the mammalian electron transfer chain is composed of at least 43 protein subunits, of which 7 are encoded by mtDNA. It catalyzes the transfer of electrons from NADH to ubiquinone and translocates protons from the mitochondrial matrix to the intermembrane space. It may also play direct roles in the mitochondrial permeability transition and in cell death pathways. Despite the limitations of current complex I assays, biochemical studies have suggested the presence of a mild, systemic defect of complex I in Parkinson's disease (PD). Recent experimental work has modeled this abnormality using rotenone to systemically inhibit complex I. Chronic rotenone exposure accurately recapitulated the pathological, biochemical, and behavioral features of PD. Thus, relatively subtle complex I abnormalities--either genetic or acquired--may be central to the pathogenesis of PD.
Greenamyre
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JT
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. jgreena@emory.edu
Sherer
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TB
Betarbet
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Panov
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D004579:Electron Transport; D042967:Electron Transport Complex I; D015386:Hazardous Substances / Q000009:adverse effects; D006801:Humans; D046911:Macromolecular Substances; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D015386:Hazardous Substances; D046911:Macromolecular Substances; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I