Ubiquinone (UQ or Coenzyme Q) is a lipid found in all cellular membranes. It is involved in multiple cellular processes, either directly or through its effect on the redox status of the cell.
clk-1 encodes a highly conserved hydroxylase that is required for UQ biosynthesis (1).
clk-1 mutants are devoid of UQ, and instead accumulate the UQ precursor, demethoxyubiquinone (DMQ) (2). Under normal culture conditions,
clk-1 mutants are viable and healthy, presumably because they contain DMQ (3), which can partially replace UQ, and because they can use dietary UQ obtained from their bacterial food source (4). However,
clk-1 mutants have slow development, reproduction and behaviors, a decreased brood size and an extended lifespan (5). Furthermore, in the absence of dietary UQ the mutants transiently arrest development, and grow up to become sterile adults after resuming development (6). Notably, animals carrying the missense allele
clk-1(
e2519), which produce a full length mutant protein (7), have a much less severe phenotype when compared to animals carrying the null mutation
clk-1(
qm30) (5), even though both mutants are completely devoid of UQ (2, 4). This suggests that, in addition to its function in UQ biosynthesis, CLK-1 could have another function that would not be entirely abolished by the
e2519 mutation. In order to understand the pleiotropic effect of
clk-1 mutations as well as the difference in severity of the two mutant alleles, we have been carrying out several suppressor screens on different aspects of the phenotypes produced by
clk-1 mutations (8, 9). We have recently carried out screens for suppressors of the slow growth phenotype of
clk-1 mutants on UQ+ bacteria as well as for suppressors of the growth arrest and sterility on UQ- bacteria. To date we have isolated nine mutants. All mutations are dominant,
e2519-specific, suppress the dietary dependence, and map to more than 4 distinct loci. We will be presenting our progress in the phenotypic and molecular characterization of these mutants. (1).J. J. Ewbank et al., 1997. Science 275, 980-3. (2).H. Miyadera et al. , 2001. J Biol Chem 276, 7713-6. (3).A. K. Hihi et al., 2002. J Biol Chem 277, 2202-6. (4).T. Jonassen et al., 2001. PNAS 98, 421-6. (5).A. Wong et al., 1995. Genetics 139, 1247-59. (6).J. Burgess et al., 2003. J Biol Chem 278, 49555-62. (7).A. K. Hihi et al., 2003. J Biol Chem 278, 41013-8. (8).R. Branicky et al., 2001. Genetics 159, 997-1006. (9).Y. Shibata et al., 2003. Science 302, 1779-82.