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J. Biol. Chem., Vol. 278, Issue 42, 41013-41018, October 17, 2003

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Sensitivity of Caenorhabditis elegans clk-1 Mutants toUbiquinone Side-chain Length Reveals Multiple Ubiquinone-dependent Processes^*

Abdelmadjid K. Hihi, Hania Kébir and Siegfried Hekimi 

From the Department of Biology, McGill University, Montreal, Québec H3A 1B1, Canada

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 life span. 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, 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.

Received for publication, May 13, 2003 , and in revised form, July 22, 2003.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

A Canadian Institutes of Health Research investigator. To whom correspondence should be sent: Dept. of Biology, McGill University, 1205 Dr. Penfield, Montreal, Québec H3A 1B1, Canada. Tel.: 514-398-6440; Fax: 514-398-1674; E-mail: siegfried.hekimi{at}mcgill.ca.

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