Authors: Jonassen T; Larsen PL; Clarke CF
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.Keywords: Aging/genetics/*physiology; Animals; Caenorhabditis elegans/genetics/growth & development/metabolism/*physiology; *Caenorhabditis elegans Proteins; Culture Media; Diet; Escherichia coli/chemistry/genetics; Glycolysis; Helminth Proteins/genetics/*physiology; Humans; Infertility/genetics; Larva; Longevity/genetics/*physiology; Mitochondria/metabolism; Nutritional Requirements; Oxidative Phosphorylation; Protein Isoforms/genetics/physiology; Rats; Species Specificity; Stress, Physiological/metabolism; Ubiquinone/analogs & derivatives/analysis/*physiology
Journal: Proceedings of the National Academy of Sciences of the United States of America
Date: Jan. 3, 2001
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Jonassen T, Larsen PL, Clarke CF (2001) A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants. Proceedings of the National Academy of Sciences of the United States of America 98: 421-6.