Heat shock-induced autophagy has cargo selectivity in Saccharomyces cerevisiae.

Mechanisms aimed at recovering from heat-induced damage are closely associated with the organism's ability to survive extreme temperature exposure. In such a scenario, we show that autophagy, as a cytoprotective mechanism, ensures recovery and viability after induced heat stress in Saccharomyces cerevisiae. Our findings indicate that heat shock triggers the targeted degradation of ubiquitinated protein aggregates, mediated by the macroaggrephagy receptor Cue5. Moreover, heat stress induces the turnover of the aggrephagy receptor Cct2 and the polyglutamine repeats of the HTT (huntingtin) protein (polyQ-HTT). Notably, even though Cct2 and polyQ-HTT degradation is vacuole-dependent, it is mediated autonomously of canonical autophagy pathways. Collectively, this study demonstrates a novel role of autophagy in maintaining protein homeostasis after heat stress in yeast and provides insights into the potential medical applications of heat treatment.Abbreviations: Atg1: AuTophaGy related 1; Atg7: AuTophaGy related 7; Atg8: AuTophaGy related 8; Atg13: AuTophaGy related 13; Atg15: AuTophaGy related 15; Cct2: Chaperonin Containing TCP-1 2; CMA: chaperone-mediated autophagy; Cue5: Coupling of Ubiquitin conjugation to ER degradation 5; GFP: green fluorescent protein; HS: heat shock/stress; HTT: huntingtin; Pep4: carboxyPEPtidase Y-deficient 4; polyQ: polyglutamine; RFP: red fluorescent protein.