ubiquinone and 5-demethoxyubiquinone-9

Ubiquinone (UQ) (coenzyme Q) is a lipophilic redox-active molecule that functions as an electron carrier in the mitochondrial electron transport chain. Electron transfer via UQ involves the formation of semiubiquinone radicals, which causes the generation of superoxide radicals upon reaction with oxygen. In the reduced form, UQ functions as a lipid-soluble antioxidant, and protects cells from lipid peroxidation. Thus, UQ is also important as a lipophilic regulator of oxidative stress. Recently, a study on long-lived clk-1 mutants of Caenorhabditis elegans demonstrated that biosynthesis of UQ is dramatically altered in mutant mitochondria. Demethoxy ubiquinone (DMQ), that accumulates in clk-1 mutants in place of UQ, may contribute to the extension of life span. Here we elucidate the possible mechanisms of life span extension in clk-1 mutants, with particular emphasis on the electrochemical property of DMQ. Recent findings on the biochemical function of CLK-1 are also discussed.

Topics: Aging; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Helminth Proteins; Models, Biological; Mutation; Ubiquinone

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In the

Topics: Animals; Brain; Disease Models, Animal; Energy Metabolism; Histocytochemistry; Hydroxybenzoates; Mice; Mitochondrial Encephalomyopathies; Neuroprotective Agents; Salicylic Acid; Survival Analysis; Treatment Outcome; Ubiquinone

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.

Topics: Animals; Ascorbic Acid; Caenorhabditis elegans; Electron Transport Complex I; Electron Transport Complex II; Glutamic Acid; Hydroquinones; Malates; Mitochondria; Mutation; Oxidative Phosphorylation; Pyruvic Acid; Quinones; Substrate Specificity; Tetramethylphenylenediamine; Time Factors; Ubiquinone

Topics: Aluminum; Animals; Benzoates; Carbon Isotopes; Chromatography; Chromatography, Gel; Chromatography, Thin Layer; Isotope Labeling; Kinetics; Liver; Male; Mass Spectrometry; Methionine; Mevalonic Acid; Perfusion; Phenols; Rats; Saccharomyces cerevisiae; Spectrophotometry; Tritium; Ubiquinone; Ultraviolet Rays