coq7/clk-1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q
Daisuke Nakai
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan
Search for more papers by this authorTakahiko Shimizu
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorHidetoshi Nojiri
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorSatoshi Uchiyama
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorHideo Koike
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorMayumi Takahashi
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorKatsuiku Hirokawa
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan
Search for more papers by this authorCorresponding Author
Takuji Shirasawa
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Dr Takuji Shirasawa, Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173–0015, Japan. Tel.: +813 3964 3241; fax: +813 3579 4776; e-mail: [email protected]Search for more papers by this authorDaisuke Nakai
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan
Search for more papers by this authorTakahiko Shimizu
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorHidetoshi Nojiri
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorSatoshi Uchiyama
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorHideo Koike
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorMayumi Takahashi
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Search for more papers by this authorKatsuiku Hirokawa
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan
Search for more papers by this authorCorresponding Author
Takuji Shirasawa
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan
Dr Takuji Shirasawa, Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173–0015, Japan. Tel.: +813 3964 3241; fax: +813 3579 4776; e-mail: [email protected]Search for more papers by this authorSummary
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 CoQ8 from Escherichia coli and demethoxyubiquinone 9 (DMQ9) instead of CoQ9. 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 CoQ9, 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.
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