Mouse homologue of coq7/clk-1, longevity gene in Caenorhabditis elegans, is essential for coenzyme Q synthesis, maintenance of mitochondrial integrity, and neurogenesis

coq7/clk-1 was isolated from a long-lived militant of Caenorhabditis elegan s, which showed sluggish behavior and an extended life span. Mouse coq7 is homologous to Saccharomyces cerevisiae coq7/cat5 that is required for biosy nthesis of coenzyme Q (CoQ), an essential cofactor in mitochondrial respira tion. Here we generated COQ7-deficient mice to investigate the biological r ole of COQ7 in mammals. COQ7-deficient mouse embryos failed to survive beyo nd embryonic day 10.5, exhibiting small-sized body and delayed embryogenesi s. Morphological studies showed that COQ7-deficient neuroepithelial. cells failed to show the radial arrangement in the developing cerebral wall, abor ting neurogenesis at E10.5. Electron microscopic analysis further showed th e enlarged mitochondria with vesicular cristae and enlarged lysosomes fille d with disrupted membranes, which is consistent with mitochondriopathy. Bio chemical analysis demonstrated that COQ7-deficient embryos failed to synthe size CoQ(9), but instead yielded demethoxyubiquinone 9 (DMQ(9)). Cultured e mbryonic cells from COQ7-deficient mice were rescued by adding bovine fetal serum in vitro, but exhibited slowed cell proliferation, which resembled t o the phenotype of clk-1 with delayed cell divisions. The result implied th e essential role of coq7 in CoQ synthesis, maintenance of mitochondrial int egrity, and neurogenesis in mice. (C) 2001 Elsevier Science.