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Mouse Homologue of coq7/clk-1, Longevity Gene in Caenorhabditis elegans, Is Essential for Coenzyme Q Synthesis, Maintenance of Mitochondrial Integrity, and Neurogenesis

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Abstract

coq7/clk-1 was isolated from a long-lived mutant of Caenorhabditis elegans, which showed sluggish behavior and an extended life span. Mouse coq7 is homologous to Saccharomyces cerevisiae coq7/cat5 that is required for biosynthesis of coenzyme Q (CoQ), an essential cofactor in mitochondrial respiration. Here we generated COQ7-deficient mice to investigate the biological role of COQ7 in mammals. COQ7-deficient mouse embryos failed to survive beyond embryonic day 10.5, exhibiting small-sized body and delayed embryogenesis. Morphological studies showed that COQ7-deficient neuroepithelial cells failed to show the radial arrangement in the developing cerebral wall, aborting neurogenesis at E10.5. Electron microscopic analysis further showed the enlarged mitochondria with vesicular cristae and enlarged lysosomes filled with disrupted membranes, which is consistent with mitochondriopathy. Biochemical analysis demonstrated that COQ7-deficient embryos failed to synthesize CoQ9, but instead yielded demethoxyubiquinone 9 (DMQ9). Cultured embryonic cells from COQ7-deficient mice were rescued by adding bovine fetal serum in vitro, but exhibited slowed cell proliferation, which resembled to the phenotype of clk-1 with delayed cell divisions. The result implied the essential role of coq7 in CoQ synthesis, maintenance of mitochondrial integrity, and neurogenesis in mice.

References (31)

  • L Ernster et al.

    Biochemical, physiological and medical aspects of ubiquinone function

    Biochim. Biophys. Acta

    (1995)
  • C Santos-Ocana et al.

    Coenzyme Q6 and iron reduction are responsible for the extracellular ascorbate stabilization at the plasma membrane of Saccharomyces cerevisiae

    J. Biol. Chem.

    (1998)
  • B Lakowski et al.

    Determination of life-span in Caenorhabditis elegans by four clock genes

    Science

    (1996)
  • A Wong et al.

    Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing

    Genetics

    (1995)
  • J.J Ewbank et al.

    Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1

    Science

    (1997)

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