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CLK‐1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans
Author(s) -
Felkai S.,
Ewbank J.J.,
Lemieux J.,
Labbé J.C,
Brown G.G.,
Hekimi S
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.7.1783
Subject(s) - biology , caenorhabditis elegans , mitochondrion , mutant , microbiology and biotechnology , respiration , genetics , cellular respiration , gene , botany
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.