title: coq7/clk-1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q.
abstract: coq7/clk-1 was isolated from a long-lived mutant of Caenorhabditis elegans, and shows sluggish behaviours and an extended lifespan. In C. elegans and Saccharomyces cerevisiae, coq7/clk-1 is required for the biosynthesis of coenzyme Q (CoQ), an essential co-factor in mitochondrial respiration. The clk-1 mutant contains dietary CoQ(8) from Escherichia coli and demethoxyubiquinone 9 (DMQ9) instead of CoQ(9). In a previous study, we generated COQ7-deficient mice by targeted disruption of the coq7 gene and reported that mouse coq7/clk-1 is also essential for CoQ synthesis, maintenance of mitochondrial integrity and neurogenesis. In the present study, we rescued COQ7-deficient mice from embryonic lethality and established a mouse model with decreased CoQ level by transgene expression of COQ7/CLK-1. A biochemical analysis showed a concomitant decrease in CoQ(9), mitochondrial respiratory enzyme activity and the generation of reactive oxygen species (ROS) in the mitochondria of CoQ-insufficient mice. This implied that the depressed activity of respiratory enzymes and the depressed production of ROS may play a physiological role in the control of lifespan in mammalian species and of C. elegans.
authors.affiliation: Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakai
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nojiri
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Koike
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Katsuiku
authors.initials: K
authors.lastname: Hirokawa
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D019069:Cell Respiration / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D014451:Ubiquinone / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D013384:Succinate Cytochrome c Oxidoreductase; C030777:ubiquinone 7