Transient intracellular acidification regulates the core transcriptional heat shock response

Abstract

Heat shock induces a conserved transcriptional program regulated by heat shock factor 1 (Hsf1) in eukaryotic cells. Activation of this heat shock response is triggered by heat-induced misfolding of newly synthesized polypeptides, and so has been thought to depend on ongoing protein synthesis. Here, using the budding yeast Saccharomyces cerevisiae, we report the discovery that Hsf1 can be robustly activated when protein synthesis is inhibited, so long as cells undergo cytosolic acidification. Heat shock has long been known to cause transient intracellular acidification which, for reasons which have remained unclear, is associated with increased stress resistance in eukaryotes. We demonstrate that acidification is required for heat shock response induction in translationally inhibited cells, and specifically affects Hsf1 activation. Physiological heat-triggered acidification also increases population fitness and promotes cell cycle reentry following heat shock. Our results uncover a previously unknown adaptive dimension of the well-studied eukaryotic heat shock response.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE143292 and GSE152916. Raw and processed flow cytometry data, raw qPCR and translation data to reproducedoi:10.5061/dryad.zgmsbcc6v.

The following data sets were generated

Article and author information

Author details

  1. Catherine G Triandafillou

    Biophysical Sciences Graduate Program, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6715-3795
  2. Christopher D Katanski

    Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Aaron R Dinner

    Graduate Program in Biophysical Sciences, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8328-6427
  4. David Allan Drummond

    Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    For correspondence
    dadrummond@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7018-7059

Funding

National Institutes of Health (GM126547)

  • David Allan Drummond

National Institutes of Health (GM127406)

  • David Allan Drummond

Army Research Office (W911NF-14-1-0411)

  • David Allan Drummond

National Institutes of Health (GM109455)

  • Aaron R Dinner

National Institutes of Health (T32EB009412)

  • Christopher D Katanski

National Institutes of Health (T32GM007183)

  • Catherine G Triandafillou

National Science Foundation (DGE-1144082)

  • Catherine G Triandafillou

National Institutes of Health (GM136381)

  • Aaron R Dinner

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

Reviewing Editor

  1. Kevin J Verstrepen, VIB-KU Leuven Center for Microbiology, Belgium

Version history

  1. Received: January 4, 2020
  2. Accepted: August 7, 2020
  3. Accepted Manuscript published: August 7, 2020 (version 1)
  4. Version of Record published: August 26, 2020 (version 2)

Copyright

© 2020, Triandafillou 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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  1. Catherine G Triandafillou
  2. Christopher D Katanski
  3. Aaron R Dinner
  4. David Allan Drummond
(2020)
Transient intracellular acidification regulates the core transcriptional heat shock response
eLife 9:e54880.
https://doi.org/10.7554/eLife.54880

Share this article

https://doi.org/10.7554/eLife.54880

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