Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Peroxiredoxins are H2O2scavenging enzymes that also carry out H2O2signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2and extending lifespan upon caloric restriction. We show here that Tsa1 effects both these functions not by scavenging H2O2, but by repressing the nutrient signaling Ras-cAMP-PKA pathway at the level of the protein kinase A (PKA) enzyme. Tsa1 stimulates sulfenylation of cysteines in the PKA catalytic subunit by H2O2and a significant proportion of the catalytic subunits are glutathionylated on two cysteine residues. Redox modification of the conserved Cys243 inhibits the phosphorylation of a conserved Thr241 in the kinase activation loop and enzyme activity, and preventing Thr241 phosphorylation can overcome the H2O2sensitivity of Tsa1-deficient cells. Results support a model of aging where nutrient signaling pathways constitute hubs integrating information from multiple aging-related conduits, including a peroxiredoxin-dependent response to H2O2.
All Related Versions
Funding Information
  • Cancerfonden (2017-778)
  • Vetenskapsrådet (NT 2011-5170)
  • Olle Engkvists Stiftelse (20120620)
  • Carl Tryggers Stiftelse för Vetenskaplig Forskning (CTS 11:306)
  • Carl Tryggers Stiftelse för Vetenskaplig Forskning (CTS 13:277)
  • Agence Nationale de la Recherche (PrxAge)
  • Agence Nationale de la Recherche (ERRed2)
  • Vetenskapsrådet (NT 2019-03937)
  • Knut och Alice Wallenbergs Stiftelse (2017-0091)
  • Knut och Alice Wallenbergs Stiftelse (2015-0272)

This publication has 84 references indexed in Scilit: