Stress-Associated Intracellular Acidification Is Adaptive

Exposure to high temperatures induces many changes in cells, including the induction of a transcriptional program regulated by the highly-conserved transcription factor Heat Shock Factor 1 (Hsf1). In a wide range of eukaryotes, stress also triggers transient intracellular acidification which, by unknown mechanisms, is associated with increased survival. Activation of the Hsf1-mediated heat shock response can be triggered by misfolding of newly synthesized polypeptides, and so has been thought to depend on ongoing protein synthesis. I have discovered that even in the absence of ongoing translation, heat-shock-associated cytosolic acidification specifically promotes the activation of Hsf1 in budding yeast. Additionally, preventing cells from transiently acidifying during heat shock compromises fitness, demonstrating that intracellular acidification is adaptive. These results imply the existence of non-canonical triggers for the response and additional contributions to cellular fitness beyond the repair of stress-induced damage.