Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1.
The long-lived mutant of Caenorhabditis elegans, clk-1, is unable to synthesize ubiquinone, CoQ(9). Instead, the mutant accumulates demethoxyubiquinone(9) and small amounts of rhodoquinone(9) as well as dietary CoQ(8). We found a profound defect in oxidative phosphorylation, a test of integrated mitochondrial function, in clk-1 mitochondria fueled by NADH-linked electron donors, i.e. complex I-dependent substrates. Electron transfer from complex I to complex III, which requires quinones, is severely depressed, whereas the individual complexes are fully active. In contrast, oxidative phosphorylation initiated through complex II, which also requires quinones, is completely normal. Here we show that complexes I and II differ in their ability to use the quinone pool in clk-1. This is the first direct demonstration of a differential interaction of complex I and complex II with the endogenous quinone pool. This study uses the combined power of molecular genetics and biochemistry to highlight the role of quinones in mitochondrial function and aging.
Departments of Anesthesiology and Genetics, University Hospitals and Case Western Reserve University, Cleveland, Ohio 44106, USA.
Ernst-Bernhard
EB
Kayser
Margaret M
MM
Sedensky
Phil G
PG
Morgan
Charles L
CL
Hoppel
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D042963:Electron Transport Complex II / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006873:Hydroquinones / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D010085:Oxidative Phosphorylation; D019289:Pyruvic Acid / Q000378:metabolism; D011809:Quinones / Q000378:metabolism; D013379:Substrate Specificity; D013772:Tetramethylphenylenediamine / Q000378:metabolism; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism
D006873:Hydroquinones; D008293:Malates; D011809:Quinones; D014451:Ubiquinone; D018698:Glutamic Acid; C000866:5-demethoxyubiquinone-9; C030298:malic acid; D019289:Pyruvic Acid; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; C003304:rhodoquinone; C030571:ubiquinone 9; D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid; C016421:duroquinol