title: Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae.
abstract: Caloric restriction (CR) extends the life span of organisms ranging from yeast to primates. Here, we show that the thiol-dependent peroxiredoxin Tsa1 and its partner sulfiredoxin, Srx1, are required for CR to extend the replicative life span of yeast cells. Tsa1 becomes hyperoxidized/inactive during aging, and CR mitigates such oxidation by elevating the levels of Srx1, which is required to reduce/reactivate hyperoxidized Tsa1. CR, by lowering cAMP-PKA activity, enhances Gcn2-dependent SRX1 translation, resulting in increased resistance to H(2)O(2) and life span extension. Moreover, an extra copy of the SRX1 gene is sufficient to extend the life span of cells grown in high glucose concentrations by 20% in a Tsa1-dependent and Sir2-independent manner. The data demonstrate that Tsa1 is required to ensure yeast longevity and that CR extends yeast life span, in part, by counteracting age-induced hyperoxidation of this peroxiredoxin.
authors: CMB, University of Gothenburg, Medicinaregatan 9C, S-413 90 Göteborg, Sweden. mikael.molin@cmb.gu.se
authors: Mikael
authors: M
authors: Molin
authors: Junsheng
authors: J
authors: Yang
authors: Sarah
authors: S
authors: Hanzén
authors: Michel B
authors: MB
authors: Toledano
authors: Jean
authors: J
authors: Labarre
authors: Thomas
authors: T
authors: Nyström
mesh_terms: D031204:Caloric Restriction; D006861:Hydrogen Peroxide / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; D050862:Oxidoreductases Acting on Sulfur Group Donors; C479426:SRX1 protein, S cerevisiae