title: SOD2 functions downstream of Sch9 to extend longevity in yeast.
abstract: 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.
authors.affiliation: Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-0191, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Fabrizio
authors.forename: Lee-Loung
authors.initials: LL
authors.lastname: Liou
authors.forename: Vanessa N
authors.initials: VN
authors.lastname: Moy
authors.forename: Alberto
authors.initials: A
authors.lastname: Diaspro
authors.forename: Joan Selverstone
authors.initials: JS
authors.lastname: Valentine
authors.forename: Edith Butler
authors.initials: EB
authors.lastname: Gralla
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000154:Aconitate Hydratase; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase; D014157:Transcription Factors; D018631:ras Proteins; D000099156:Superoxide Dismutase 2; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; C071569:SCH9 protein kinase; C489015:RAS2 protein, S cerevisiae