Open Accesscoq7/clk‐1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q
Author(s) -
Nakai Daisuke,
Shimizu Takahiko,
Nojiri Hidetoshi,
Uchiyama Satoshi,
Koike Hideo,
Takahashi Mayumi,
Hirokawa Katsuiku,
Shirasawa Takuji
Publication year - 2004
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9728.2004.00116.x
Subject(s) - biology , coenzyme q – cytochrome c reductase , mitochondrion , caenorhabditis elegans , reactive oxygen species , mitochondrial ros , mutant , mitochondrial respiratory chain , respiratory chain , alternative oxidase , transgene , biochemistry , microbiology and biotechnology , gene , cytochrome c
Summary 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 .