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.
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Transient intracellular acidification regulates the core transcriptional heat shock responseDryad Digital Repository, doi:10.5061/dryad.zgmsbcc6v.
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Transient intracellular acidification regulates the core transcriptional heat shock responseNCBI Gene Expression Omnibus, GSE143292.
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Transient intracellular acidification regulates the core transcriptional heat shock responseNCBI Gene Expression Omnibus, GSE152916.
Article and author information
Author details
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.
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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