coq7/clk-1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q.
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.
Nakai
Daisuke
D
Department of Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan.
Shimizu
Takahiko
T
Nojiri
Hidetoshi
H
Uchiyama
Satoshi
S
Koike
Hideo
H
Takahashi
Mayumi
M
Hirokawa
Katsuiku
K
Shirasawa
Takuji
T
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*
D029742:Caenorhabditis elegans Proteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D013384:Succinate Cytochrome c Oxidoreductase; C030777:ubiquinone 7