Phase separation of a yeast prion protein promotes cellular fitness

TLDR

Liquid‑liquid phase separation enables cells to sense and respond to subtle changes in pH, temperature, or salt, potentially sequestering proteins in protective compartments. The authors used the yeast translation termination factor Sup35 to model a phase‑separation–driven stress response. Lowering pH caused Sup35 to phase‑separate into liquid droplets that hardened into gels sequestering the factor, while raising pH dissolved the gels and restored translation, suggesting that gel‑mediated protection of Sup35 may enhance yeast fitness after stress. Published in Science (issue p.

Abstract

Biophysical responses of proteins to stress Much recent work has focused on liquid-liquid phase separation as a cellular response to changing physicochemical conditions. Because phase separation responds critically to small changes in conditions such as pH, temperature, or salt, it is in principle an ideal way for a cell to measure and respond to changes in the environment. Small pH changes could, for instance, induce phase separation of compartments that store, protect, or inactivate proteins. Franzmann et al. used the yeast translation termination factor Sup35 as a model for a phase separation–induced stress response. Lowering the pH induced liquid-liquid phase separation of Sup35. The resulting liquid compartments subsequently hardened into gels, which sequestered the termination factor. Raising the pH triggered dissolution of the gels, concomitant with translation restart. Protecting Sup35 in gels could provide a fitness advantage to recovering yeast cells that must restart the translation machinery after stress. Science , this issue p. eaao5654