title: A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants.
abstract: Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result in slowed development, sluggish adult behaviors, and an increased lifespan. CLK-1 is a mitochondrial polypeptide with sequence and functional conservation from human to yeast. Coq7p, the Saccharomyces cerevisiae homologue, is essential for ubiquinone (coenzyme Q or Q) synthesis and therefore respiration. However, based on assays of respiratory function, it has been reported that the primary defect in the C. elegans clk-1 mutants is not in Q biosynthesis. How do the clk-1 mutant worms have essentially normal rates of respiration, when biochemical studies in yeast suggest a Q deficiency? Nematodes are routinely fed Escherichia coli strains containing a rich supply of Q. To study the Q synthesized by C. elegans, we cultured worms on an E. coli mutant that lacks Q and found that clk-1 mutants display early developmental arrest from eggs, or sterility emerging from dauer stage. Provision of Q-replete E. coli rescues these defects. Lipid analysis showed that clk-1 worms lack the nematode Q(9) isoform and instead contain a large amount of a metabolite that is slightly more polar than Q(9). The clk-1 mutants also have increased levels of Q(8), the E. coli isoform, and rhodoquinone-9. These results show that the clk-1 mutations result in Q auxotrophy evident only when Q is removed from the diet, and that the aging and developmental phenotypes previously described are consistent with altered Q levels and distribution.
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jonassen
authors.forename: P L
authors.initials: PL
authors.lastname: Larsen
authors.forename: C F
authors.initials: CF
authors.lastname: Clarke
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D003470:Culture Media; D004032:Diet; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D006019:Glycolysis; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007246:Infertility / Q000235:genetics; D007814:Larva; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D009751:Nutritional Requirements; D010085:Oxidative Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D051381:Rats; D013045:Species Specificity; D013312:Stress, Physiological / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000032:analysis / Q000502:physiology*
chemical_list: C104339:CLK-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D003470:Culture Media; D015801:Helminth Proteins; D020033:Protein Isoforms; D014451:Ubiquinone; C003304:rhodoquinone