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A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide

View ORCID ProfileBasile Jacquel, Audrey Matifas, View ORCID ProfileGilles Charvin
doi: https://doi.org/10.1101/2021.04.23.440814
Basile Jacquel
1Department of Developmental Biology and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
2Centre National de la Recherche Scientifique, UMR7104, Illkirch, France
3Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France
4Université de Strasbourg, Illkirch, France
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  • For correspondence: charvin@igbmc.fr jacquelb@igbmc.fr
Audrey Matifas
1Department of Developmental Biology and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
2Centre National de la Recherche Scientifique, UMR7104, Illkirch, France
3Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France
4Université de Strasbourg, Illkirch, France
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Gilles Charvin
1Department of Developmental Biology and Stem Cells, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
2Centre National de la Recherche Scientifique, UMR7104, Illkirch, France
3Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France
4Université de Strasbourg, Illkirch, France
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  • ORCID record for Gilles Charvin
  • For correspondence: charvin@igbmc.fr jacquelb@igbmc.fr
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Abstract

In response to environmental stress, cellular defense strategies may be divided into two categories: those, as in homeostatic systems, that seek to maintain cell proliferation by degrading the stressor (i.e., resistance); and those that ensure cell survival (i.e. tolerance), even if this is often at the expense of cell proliferation. In this study, we have explored the genetic bases of the antagonism between resistance and tolerance during the response to hydrogen peroxide (H2O2) in budding yeast. We show that inactivation of protein kinase A (PKA) by H2O2 signaling induces an abrupt transition from normal homeostatic function to a stress-tolerant state by protecting the growth machinery, hence maximizing cellular fitness in a changing environment. This model system paves the way for developing antiproliferative strategies that target both resistance and tolerance mechanisms to prevent relapse.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted April 26, 2021.
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A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide
Basile Jacquel, Audrey Matifas, Gilles Charvin
bioRxiv 2021.04.23.440814; doi: https://doi.org/10.1101/2021.04.23.440814
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A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide
Basile Jacquel, Audrey Matifas, Gilles Charvin
bioRxiv 2021.04.23.440814; doi: https://doi.org/10.1101/2021.04.23.440814

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