Disease relevance of clk-1

• To test the effect of isoprene tail length, N2 and clk-1 animals were fed E. coli engineered to produce Q7, Q8, Q9, or Q10 [1].
• These results suggest that the uptake and transport of dietary Q(8) to mitochondria prevent the arrest and sterility phenotypes of clk-1 mutants and that DMQ is not functionally equivalent to Q [2].

High impact information on clk-1

• A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants [3].
• The gene clk-1 was identified, and the cloned gene complemented the clk-1 phenotypes and restored normal longevity [4].
• Inactivation of the Caenorhabditis elegans gene clk-1, which is required for ubiquinone biosynthesis, increases lifespan by an insulin signaling-independent mechanism [5].
• Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result in an average slowing of a variety of developmental and physiological processes, including the cell cycle, embryogenesis, post-embryonic growth, rhythmic behaviors and aging [6].
• Three of these genes, age-1, daf-2 and clk-1, have now been cloned [7].

Chemical compound and disease context of clk-1

• We have identified by RNA interference (RNAi) eight genes, including clk-1, involved in ubiquinone biosynthesis in C. elegans feeding animals with dsRNA-containing Escherichia coli HT115 strains [8].
• The Caenorhabditis elegans clk-1 mutants lack coenzyme Q(9) and instead accumulate the biosynthetic intermediate demethoxy-Q(9) (DMQ(9)). clk-1 animals grow to reproductive adults, albeit slowly, if supplied with Q(8)-containing Escherichia coli [2].

Biological context of clk-1

• Mutation in the transcription factor daf-16 suppressed the Age and ATP phenotypes, but not the reduction of respiration rate imparted by mutation in clk-1 [9].
• Moreover, these mutant alleles both extend life span and increase resistance to ultraviolet (UV) radiation [11], heat [12], and oxidative stress [13-15], though the stress resistance of clk-1 is controversial [10].
• The differential fertility of clk-1 mutant nematodes fed Q isoforms may result from changes in Q localization, altered recognition by Q-binding proteins, and/or potential defects in mitochondrial function resulting from the mutant CLK-1 polypeptide itself [1].
• Rates of oxidative phosphorylation were decreased in all three mutants, but the ROS damage was decreased only in clk-1 [11].
• In contrast, a spe-26 mutant had a tenfold lower mortality until approximately 2 weeks of age but ultimately achieved a higher mortality, whereas clk-1 mutants show slightly higher mortality than wild type during the fertile period, early in life, but ultimately level off at lower mortality [12].

Anatomical context of clk-1

• The content of Q7 in the mitochondria of clk-1 animals was decreased relative to Q8, suggesting less effective transport of Q7 to the mitochondria, impaired retention, or decreased stability [1].
• Our results indicate that DMQ9 cannot achieve the same redox role of Q9 in plasma membrane, suggesting that proportion of all these Q isoforms in plasma membrane must be an important factor in establishing the clk-1 mutant phenotype [13].

Associations of clk-1 with chemical compounds

• On the contrary, phenotype of C. elegans coq-7/clk-1 mutants may be a unique phenotype than can not generalize to mutants in ubiquinone biosynthesis [14].
• Caenorhabditis elegans clk-1 mutants lack coenzyme Q9 and accumulate the biosynthetic intermediate demethoxy-Q9 [1].
• Here we show that complexes I and II differ in their ability to use the quinone pool in clk-1 [15].
• Caenorhabditis elegans clk-1 mutants cannot produce coenzyme Q(9) and instead accumulate demethoxy-Q(9) (DMQ(9)) [16].
• Development and fertility in Caenorhabditis elegans clk-1 mutants depend upon transport of dietary coenzyme Q8 to mitochondria [2].

Other interactions of clk-1

• We tested this hypothesis by measuring respiration rates, light production capacities (a measure of metabolic potential) and ATP levels in various strains harbouring mutant alleles of the Clk genes clk-1 and gro-1 and of three other genes that interact with the Clk genes [9].
• Each of three well-studied mutants (age-1, clk-1, and spe-26) alters age-specific mortality rates in a fashion unique to itself [17].
• In C. elegans, coq-7/clk-1 but not coq-3 mutants live longer than wild type showing a 'slowed' phenotype [14].
• 1. Similarly, there was partial requirement for aak-2 in lifespan extension by mitochondrial mutations (isp-1 and clk-1) [18].
• In this study, we demonstrated that the daf-2 mutation also conferred an oxidative stress resistance (Oxr) phenotype, which was also enhanced by the clk-1 mutation [19].

Analytical, diagnostic and therapeutic context of clk-1

• In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes [20].

References