Oxidative phase transition of heat shock factor-1

Abstract

Heat shock factor 1 (Hsf1) was found as a central upregulator of molecular chaperones in stress adaptation, but it has recently been rediscovered as a major component of persistent nuclear stress bodies (nSBs). When the persistently stressed cells undergo apoptosis, the phase transition of nSBs from fluid to gel-like states is proposed to be an important event in switching the cell fate from survival to death. Nonetheless, how the phase separation and transition of nSBs are driven remain unanswered. In this study, we discovered that Hsf1 formed liquid-liquid phase separation droplets in vitro, causing the assembly of Hsf1 to drive nSBs formation. Under oxidative conditions, disulfide-bonded and oligomerized Hsf1 formed gel-like and more condensed droplets, confirmed through fluorescence recovery, refractive index imaging, and light scattering. Then, on the basis of our results, we proposed that Hsf1 undergoes oxidative phase transition by sensing redox conditions potentially to drive the cell fate decision by nSBs.