Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans.
Mutations in the mev-1 and gas-1 genes of the nematode Caenorhabditis elegans render animals hypersensitive to oxygen and paraquat, and lead to premature aging. We show that both mutants overproduce superoxide anion in isolated sub-mitochondrial particles, which probably explains their hypersensitivity to oxidative stress. The daf-16 gene encodes a fork-head transcription factor that is negatively regulated by an insulin-signaling pathway. In wild-type animals, the DAF-16 protein normally resides in the cytoplasm and only becomes translocated to nuclei upon activating stimuli such as oxidative stress. Conversely, DAF-16 resides constitutively in the nuclei of mev-1 and gas-1 mutants even under normal growth conditions. Supplementation of the antioxidant coenzyme Q(10) reversed this nuclear translocation of DAF-16. Since both gas-1 and mev-1 encode subunits of electron transport chain complexes, these data illustrate how mitochondrial perturbations can impact signal transduction pathways.
Kondo
Masaki
M
Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Senoo-Matsuda
Nanami
N
Yanase
Sumino
S
Ishii
Takamasa
T
Hartman
Philip S
PS
Ishii
Naoaki
N
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D009245:NADH Dehydrogenase; C468009:GAS-1 protein, C elegans; D010100:Oxygen