Effect of Oxidative Stress on Translocation of DAF-16 in Oxygen-Sensitive Mutants, mev-1 and gas-1 of Caenorhabditis Elegans

Mech Ageing Dev. Jun-Jul 2005;126(6-7):637-41. doi: 10.1016/j.mad.2004.11.011. Epub 2005 Jan 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Aging, Premature / genetics
  • Aging, Premature / metabolism*
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Forkhead Transcription Factors
  • Mutation*
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism
  • Oxidative Stress* / genetics
  • Oxygen / metabolism
  • Transcription Factors / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Transcription Factors
  • daf-16 protein, C elegans
  • NADH Dehydrogenase
  • GAS-1 protein, C elegans
  • Oxygen