SOD2 functions downstream of Sch9 to extend longevity in yeast.
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.
Fabrizio
Paola
P
Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-0191, USA.
Liou
Lee-Loung
LL
Moy
Vanessa N
VN
Diaspro
Alberto
A
Valentine
Joan Selverstone
JS
Gralla
Edith Butler
EB
Longo
Valter D
VD
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
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