Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
- University of Gothenburg, Sweden
- Chalmers University of Technology, Sweden
- University of Vienna, Austria
- CEA Saclay, France
- IBITECS, SBIGEM, CEA-Saclay, France
Abstract
Peroxiredoxins are H2O2 scavenging enzymes that also carry H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxiredoxin, Tsa1 is required for both promoting resistance to H2O2 and 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 H2O2 and 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 H2O2 sensitivity 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.
Data availability
Proteomics data have been deposited in the PRIDE repository.
Article and author information
Author details
Funding
Cancerfonden
- Mikael Molin
Vetenskapsrådet
- Mikael Molin
Stiftelsen Olle Engkvist Byggmästare
- Mikael Molin
Carl Tryggers Stiftelse för Vetenskaplig Forskning
- Mikael Molin
Agence Nationale de la Recherche (PrxAge)
- Michel B Toledano
Agence Nationale de la Recherche (ERRed2)
- Michel B Toledano
Swedish Research Council (NT 2019-03937)
- Thomas Nyström
Knut och Alice Wallenbergs Stiftelse (2017-0091 and 2015-0272)
- Thomas Nyström
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Maya Schuldiner, Weizmann Institute, Israel
Version history
- Received: June 24, 2020
- Accepted: July 8, 2020
- Accepted Manuscript published: July 14, 2020 (version 1)
- Accepted Manuscript updated: July 15, 2020 (version 2)
- Version of Record published: July 30, 2020 (version 3)
Copyright
© 2020, Roger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A
eLife 9:e60346.
https://doi.org/10.7554/eLife.60346
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