Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans

• Published in: Mechanisms of ageing and development Vol. 126; no. 6; pp. 637 - 641
• Main Authors: Kondo, Masaki, Senoo-Matsuda, Nanami, Yanase, Sumino, Ishii, Takamasa, Hartman, Philip S., Ishii, Naoaki
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.06.2005; Elsevier Science
• Subjects: Active Transport, Cell Nucleus - genetics; Aging, Premature - genetics; Aging, Premature - metabolism; Animals; Biological and medical sciences; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Nucleus - genetics; Cell Nucleus - metabolism; Coenzyme Q10; DAF-16; Development. Metamorphosis. Moult. Ageing; Forkhead Transcription Factors; Fundamental and applied biological sciences. Psychology; gas-1; mev-1; Mitochondria; Mutation; NADH Dehydrogenase - genetics; NADH Dehydrogenase - metabolism; Oxidative stress; Oxidative Stress - genetics; Oxygen - metabolism; Transcription Factors - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Oxidative stress; Mitochondria; gas-1; Coenzyme Q10; mev-1; DAF-16; Translocation; Oxygen; Senescence; Coenzyme; Caenorhabditis elegans; Vertebrata; Mammalia; Helmintha; Nemathelminthia; Mutation; Invertebrata; Nematoda
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2004.11.011

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.