1. Cell Biology
  2. Computational and Systems Biology
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Nonlinear feedback drives homeostatic plasticity in H2O2 stress response

  1. Youlian goulev  Is a corresponding author
  2. Sandrine morlot
  3. Audrey matifas
  4. Bo huang
  5. Mikael Molin
  6. Michel B Toledano
  7. Gilles Charvin  Is a corresponding author
  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, France
  2. IBITECS, SBIGEM, CEA-Saclay, France
  3. University of Gothenburg, Sweden
Research Article
  • Cited 15
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Cite this article as: eLife 2017;6:e23971 doi: 10.7554/eLife.23971

Abstract

Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time, which may restrict a cell’s ability to adapt to unanticipated environmental challenges. To bypass this limitation, cells have evolved mechanisms whereby exposure to mild stress increases their resistance to subsequent threats. However, the mechanisms responsible for such adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and microfluidics to investigate the adaptive response of budding yeast to temporally controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is a systems-level property resulting from nonlinearity of H2O2 scavenging by peroxiredoxins and our study reveals that this regulatory scheme induces a striking hormetic effect of extracellular H2O2 stress on replicative longevity. Our study thus provides a novel quantitative framework bridging the molecular architecture of a cellular homeostatic system to the emergence of nonintuitive adaptive properties.

Article and author information

Author details

  1. Youlian goulev

    Developmental biology and stem cells department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, Illkirch Cedex, France
    For correspondence
    youlian.goulev@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
  2. Sandrine morlot

    Developmental biology and stem cells department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, Illkirch Cedex, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Audrey matifas

    Developmental biology and stem cells department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, Illkirch Cedex, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Bo huang

    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:" 0000-0001-5945-7601
  5. Mikael Molin

    Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. 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.
  7. Gilles Charvin

    Developmental biology and stem cells department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, Illkirch Cedex, France
    For correspondence
    charvin@igbmc.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6852-6952

Funding

Association de recherche contre le cancer (PDF20111204470)

  • Youlian goulev

ATIP-Avenir program

  • Gilles Charvin

Fondation pour la Recherche Médicale (DEI20151234397)

  • Gilles Charvin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Naama Barkai, Weizmann Institute of Science, Israel

Publication history

  1. Received: December 6, 2016
  2. Accepted: April 14, 2017
  3. Accepted Manuscript published: April 18, 2017 (version 1)
  4. Accepted Manuscript updated: April 19, 2017 (version 2)
  5. Accepted Manuscript updated: April 27, 2017 (version 3)
  6. Version of Record published: May 19, 2017 (version 4)

Copyright

© 2017, goulev 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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