Abstract
Cellular stress induces rapid expression of genes encoding molecular chaperones. In many eukaryotes, stress also triggers transient intracellular acidification which, by unknown mechanisms, is associated with increased survival. Here, using budding yeast as a model, we discover that preventing cells from transiently acidifying during heat shock compromises induction of molecular chaperones and fitness. Prevention of acidification during stress and recovery silences induction of a canonical heat-shock protein altogether. The association between acidification, induction, and growth holds at the population and single-cell levels. Hinting at the molecular basis of these effects, the failure to acidify specifically suppresses induction of genes regulated by the conserved heat shock transcription factor Hsf1. Our results establish a central role for intracellular pH in the eukaryotic transcriptional stress response, and implicate pH-sensitive stress-sensing proteins, rather than misfolded proteins, in the activation of Hsf1 under physiological heat shock conditions.
Footnotes
↵* dadrummond{at}uchicago.edu