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

Daisuke Nakai, Shigeki Yuasa, Mayumi Takahashi, Takahiko Shimizu, Sunao Asaumi, Kyoichi Isono, Toshifumi Takao, Yo ichi Suzuki, Hidehito Kuroyanagi, Katsuiku Hirokawa, Haruhiko Koseki, Takuji Shirsawa

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)463-471
Number of pages9
JournalBiochemical and biophysical research communications
Volume289
Issue number2
DOIs
Publication statusPublished - 2001 Nov 30

Keywords

  • Coq7/clk-1
  • Electron microscopy
  • Embryogenesis
  • Knock-out mice
  • Longevity
  • Mitochondria
  • Mitochondriopathy
  • Neurogenesis
  • Transgene
  • Ubiquinone

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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