Authors: Felkai S; Ewbank JJ; Lemieux J; LabbÃ© JC; Brown GG; Hekimi S
Abstract: 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. In yeast, a CLK-1 homologue is absolutely required for ubiquinone biosynthesis and thus respiration. Here we show that CLK-1 is fully active when fused to green fluorescent protein and is found in the mitochondria of all somatic cells. The activity of mutant mitochondria, however, is only very slightly impaired, as measured in vivo by a dye-uptake assay, and in vitro by the activity of succinate cytochrome c reductase. Overexpression of CLK-1 activity in wild-type worms can increase mitochondrial activity, accelerate behavioral rates during aging and shorten life span, indicating that clk-1 regulates and controls these processes. These observations also provide strong genetic evidence that mitochondria are causally involved in aging. Furthermore, the reduced respiration of the long-lived clk-1 mutants suggests that longevity is promoted by the age-dependent decrease in mitochondrial function that is observed in most species.Keywords: Aging/genetics/physiology; Animals; Animals, Genetically Modified; Behavior, Animal/physiology; Caenorhabditis elegans/*genetics/*physiology; *Caenorhabditis elegans Proteins; Gene Expression; Genes, Helminth; Genes, Reporter; Green Fluorescent Proteins; Helminth Proteins/*genetics/*physiology; Luminescent Proteins/genetics/metabolism; Mitochondria/metabolism; Mutation; Oxygen Consumption/genetics/physiology; Recombinant Fusion Proteins/genetics/metabolism
Journal: The EMBO journal
Date: April 15, 1999
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Felkai S, Ewbank JJ, Lemieux J, LabbÃ© JC, Brown GG, Hekimi S (1999) CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans. The EMBO journal 18: 1783-92.