Figure 1. Two parallel pathways can induce the heat shock response in yeast.

The heat shock response is controlled by the heat shock transcription factor Hsf1; it is repressed (HSR_off) when conditions are stable, but rapidly induced (HSR_on) by a high temperature. In ‘nutrient-rich’ cells (top), translation is robust and thermal stress (flame) causes a subset of nascent polypeptides to misfold and aggregate, ultimately activating Hsf1 and the heat shock response. When cells are starving (and have therefore stopped translation), the heat shock response is still induced; the trigger presumably involves mature, folded proteins assembling into phase-separated structures that can recruit chaperones. Thermal stress leads to a drop in pH (blue arrow) in all cells, but only starving cells require acidification to trigger the heat shock response.