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Papers In Press, published online ahead of print July 31, 2003
Biology Dept., McGill University, Montreal, Quebec H3A 1B1
Corresponding Author: shekim1{at}po-box.mcgill.ca
Ubiquinone (coenzyme Q, or Q) is a membrane constituent, whose head group is capable of accepting and donating electrons, and whose lipidic side-chain is composed of a variable number of isoprene subunits. A possible role for Q as a dietary antioxidant for treating conditions that involve altered cellular redox states is being intensely studied. Mutations in the clk-1 gene of the nematode Caenorhabditis elegans affect numerous physiological rates including behavioral rates, developmental rates, reproduction and lifespan. clk-1 encodes a protein associated with the inner mitochondrial membrane that is necessary for Q biosynthesis in C. elegans. clk-1 mutants do not synthesize Q but accumulate demethoxyubiquinone (DMQ), a Q-synthesis intermediate that is able to partially sustain mitochondrial respiration in worms, as well as in mammals. Recently, we and others have found that exogenous Q is necessary for the fertility and development of clk-1 mutants. Here, we take advantage of the clk-1 genetic model to identify structural features of Q that are functionally important in vivo. We show that clk-1 mutants are exquisitely sensitive to the length of the side-chain of the Q they consume. We also identified differential sensitivity to Q side-chain length between null alleles of clk-1 (qm30 and qm51) and the weaker allele e2519. This allows us to propose a model where we distinguish several types of Q-dependent processes in vivo: processes that are very sensitive to Q side-chain length, and processes that are permissive to Q with shorter chains.
J. Biol. Chem, 10.1074/jbc.M305034200
Submitted on May 13, 2003
Revised on July 31, 2003
Accepted on July 31, 2003
Sensitivity of caenorhabditis elegans clk-1 mutants to ubiquinone side-chain length reveals multiple ubiquinone-dependent processes
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