TY - JOUR TI - Transient intracellular acidification regulates the core transcriptional heat shock response AU - Triandafillou, Catherine G AU - Katanski, Christopher D AU - Dinner, Aaron R AU - Drummond, D Allan A2 - Struhl, Kevin A2 - Verstrepen, Kevin J A2 - Verstrepen, Kevin J A2 - Morano, Kevin VL - 9 PY - 2020 DA - 2020/08/07 SP - e54880 C1 - eLife 2020;9:e54880 DO - 10.7554/eLife.54880 UR - https://doi.org/10.7554/eLife.54880 AB - 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. KW - heat shock KW - stress response KW - Hsf1 KW - pH KW - yeast JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -