SOD2 functions downstream of Sch9 to extend longevity in yeast

Genetics. 2003 Jan;163(1):35-46. doi: 10.1093/genetics/163.1.35.


Signal transduction pathways inactivated during periods of starvation are implicated in the regulation of longevity in organisms ranging from yeast to mammals, but the mechanisms responsible for life-span extension are poorly understood. Chronological life-span extension in S. cerevisiae cyr1 and sch9 mutants is mediated by the stress-resistance proteins Msn2/Msn4 and Rim15. Here we show that mitochondrial superoxide dismutase (Sod2) is required for survival extension in yeast. Deletion of SOD2 abolishes life-span extension in sch9Delta mutants and decreases survival in cyr1:mTn mutants. The overexpression of Sods--mitochondrial Sod2 and cytosolic CuZnSod (Sod1)--delays the age-dependent reversible inactivation of mitochondrial aconitase, a superoxide-sensitive enzyme, and extends survival by 30%. Deletion of the RAS2 gene, which functions upstream of CYR1, also doubles the mean life span by a mechanism that requires Msn2/4 and Sod2. These findings link mutations that extend chronological life span in S. cerevisiae to superoxide dismutases and suggest that the induction of other stress-resistance genes regulated by Msn2/4 and Rim15 is required for maximum longevity extension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aconitate Hydratase / metabolism
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins*
  • Mutation
  • Protein Kinases / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Superoxide Dismutase / metabolism*
  • Transcription Factors / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • DNA-Binding Proteins
  • Fungal Proteins
  • MSN2 protein, S cerevisiae
  • MSN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Protein Kinases
  • SCH9 protein kinase
  • RAS2 protein, S cerevisiae
  • ras Proteins
  • Aconitate Hydratase