Affiliations

Professor, Chemistry and Biochemistry, Biochemistry, Molecular Biology

Member, Graduate Program in Biochemistry, Molecular and Structural Biology, I3T Theme, Molecular Biology Institute

Researcher, Biochemistry, Chemical Biology, Proteomics and Bioinformatics

Coenzyme Q (also known as ubiquinone or Q) is a lipid component of cellular membranes that functions in cells as a redox-active coenzyme of both mitochondria and plasma membrane electron transport, as an essential lipid soluble antioxidant, and plays a role in apoptosis. We study the biosynthesis, regulation and function of Q in the yeast Saccharomyces cerevisiae. Our research takes advantage of a class of respiratory defective yeast mutants deficient in Q. We are characterizing the defects in these mutants by isolating and elucidating the structures of the Q biosynthetic intermediates and are characterizing both yeast and mammalian polypeptides required for Q biosynthesis. Our results suggest that yeast and higher eukaryotes share the same Q biosynthetic pathway, and that a large multi-subunit complex within the mitochondrial matrix is required for Q biosynthesis. Recently we have turned to the nematode Caenorhabditis elegans as an excellent model for genetic studies of the aging process. Gene mutations that increase life span have been identified in C. elegans that have homologs in vertebrates and appear to act by highly conserved mechanisms, and in pathways that parallel those present in humans. Mutations in the C. elegans clk-1 gene result in an extended life span, slowed development and sluggish behavior. Homology of clk-1 and COQ7 suggested that the long-lived C. elegans clk-1 mutants are defective in Q biosynthesis. Normally nematodes are provided a diet of Q-replete E. coli. In the absence of dietary Q, the clk-1 mutants display their true phenotype – growth arrest in early development and sterility when emerging from the dauer stage. These results suggest that clk-1 is essential for Q biosynthesis, and that the aging and developmental phenotypes previously described may be attributed to Q levels. Our recent studies indicate that both mean and maximum life span of wild-type nematodes fed Q-less diets is extended 60%. This life span extension is quite robust and is observed in all Age mutants tested so far, when transferred to the Q-less diet as adults. Our studies will define the metabolic alterations resulting from dietary Q, and will help determine how diet/environment and genotype interact to change longevity. Based on the strong conservation of Q function, our findings should be very relevant to aging in other organisms.

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