A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants

Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result i n slowed development, sluggish adult behaviors, and an increased lifespan. CLK-1 is a mitochondrial polypeptide with sequence and functional conservat ion from human to yeast. Coq7p, the Saccharomyces cerevisiae homologue, is essential for ubiquinone (coenzyme Q or Q) synthesis and therefore respirat ion. 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 biosyn thesis. How do the clk-1 mutant worms have essentially normal rates of resp iration, when biochemical studies in yeast suggest a Q deficiency? Nematode s 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 developmenta l arrest from eggs, or sterility emerging from dauer stage. Provision of Q- replete E. coli rescues these defects. Lipid analysis showed that clk-1 wor ms lack the nematode Qs isoform and instead contain a large amount of a met abolite that is slightly more polar than Qs. The clk-1 mutants also have in creased levels of Qs, the E, coli isoform, and rhodoquinone-9. These result s 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 p reviously described are consistent with altered Q levels and distribution.