1. Biochemistry and Chemical Biology
  2. Cell Biology
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Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A

  1. Friederike Roger
  2. Cecilia Picazo
  3. Wolfgang Reiter
  4. Marouane Libiad
  5. Chikako Asami
  6. Sarah Hanzén
  7. Chunxia Gao
  8. Gilles Lagniel
  9. Niek Welkenhuysen
  10. Jean Labarre
  11. Thomas Nyström
  12. Morten Grotli
  13. Markus Hartl
  14. Michel B Toledano
  15. Mikael Molin  Is a corresponding author
  1. University of Gothenburg, Sweden
  2. Chalmers University of Technology, Sweden
  3. University of Vienna, Austria
  4. CEA Saclay, France
  5. IBITECS, SBIGEM, CEA-Saclay, France
Research Article
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Cite this article as: eLife 2020;9:e60346 doi: 10.7554/eLife.60346

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.

Article and author information

Author details

  1. Friederike Roger

    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Cecilia Picazo

    Dept of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Wolfgang Reiter

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Marouane Libiad

    Oxidative stress and cancer laboratory, Integrative Biology and Molecular Genetics Unit (SBiGEM), CEA Saclay, Gif sur Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Chikako Asami

    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Sarah Hanzén

    Department of Chemistry and Molecular BIology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Chunxia Gao

    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Gilles Lagniel

    Oxidative Stress and Cancer Laboratory, Integrative Biology and Molecular Genetics Unit, CEA Saclay, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Niek Welkenhuysen

    Dept of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  10. Jean Labarre

    Oxidative Stress and Cancer Laboratory, Integrative Biology and Molecular Genetics Unit, CEA Saclay, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Thomas Nyström

    Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5489-2903
  12. Morten Grotli

    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3621-4222
  13. Markus Hartl

    Max F. Perutz Laboratories, University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4970-7336
  14. Michel B Toledano

    Oxidative Stress and Cancer, IBITECS, SBIGEM, CEA-Saclay, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3079-1179
  15. Mikael Molin

    Dept of Biology and Biological Engineering, Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden
    For correspondence
    mikael.molin@chalmers.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3903-8503

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

  1. Maya Schuldiner, Weizmann Institute, Israel

Publication history

  1. Received: June 24, 2020
  2. Accepted: July 8, 2020
  3. Accepted Manuscript published: July 14, 2020 (version 1)
  4. Accepted Manuscript updated: July 15, 2020 (version 2)
  5. 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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