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

Tanya Jonassen, Pamela L. Larsen, Catherine F. Clarke

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

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 Q9 isoform and instead contain a large amount of a metabolite that is slightly more polar than Q9. The clk-1 mutants also have increased levels of Q8, 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.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number2
DOIs
StatePublished - Jan 16 2001

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants'. Together they form a unique fingerprint.

Cite this