Under thermal stress, different protein quality control (PQC) strategies are activated to maintain an intact proteome, which may vary from one model system to another. Hence thermo-sensitive proteins that lose their active conformation might be refolded with the aid of chaperones or removed by the ubiquitin–proteasome system or the process of autophagy. We have recently developed thermo-sensitive reporters to study PQC in fission yeast and shown the relevance of a third adaptation strategy: the sequestration of misfolded proteins into inclusions which will prevent a rapid degradation and allow the refolding once stress ends. These protein inclusions, protein aggregate centers (PACs), contain a broad spectrum of misfolding/aggregation-prone proteins and chaperones involved in their assembly or dissolution. The chaperone couple Mas5/Ssa2 plays a crucial role in PAC formation, whereas the Hsp104 chaperone promotes their disassembly. The absence of aggregates observed in cells lacking Mas5 could be also explained by the activation of the transcription factor Hsf1 and the induction of chaperone genes, we have excluded this possibility here demonstrating that increased Hsf1 activity and the subsequent overexpression of chaperones do not prevent the assembly of protein aggregates. Protein deposition at certain locations also constitutes a tactic to inactivate proteins temporally. This is the case of Pyp1, the main phosphatase of the stress response kinase Sty1. Upon stress imposition, misfolded Pyp1 is sequestered into cytosolic protein foci while active Sty1 at the nucleus switches on the transcriptional response. In conclusion, we propose that the assembly of aggregation-like foci, PACs in fission yeast, is a crucial PQC strategy during heat stress, and that the Hsp40 chaperone Mas5 is required for PAC assembly and connects physiological and heat-shock triggered PQC.

在热应激下，不同的蛋白质质量控​​制 (PQC) 策略被激活以维持完整的蛋白质组，这可能因一个模型系统而异。因此，失去活性构象的热敏蛋白可能会在分子伴侣的帮助下重新折叠，或者被泛素-蛋白酶体系统或自噬过程去除。我们最近开发了热敏报告基因来研究裂殖酵母中的 PQC，并展示了第三种适应策略的相关性：将错误折叠的蛋白质隔离到内含物中，这将防止快速降解并在压力结束后允许重新折叠。这些蛋白质内含物，蛋白质聚集中心 (PAC)，包含广泛的错误折叠/易于聚集的蛋白质和参与其组装或溶解的分子伴侣。伴侣伴侣 Mas5/Ssa2 在 PAC 形成中起着至关重要的作用，而 Hsp104 伴侣则促进它们的分解。在缺乏 Mas5 的细胞中没有观察到聚集体也可以通过转录因子 Hsf1 的激活和伴侣基因的诱导来解释，我们在这里排除了这种可能性，证明 Hsf1 活性增加和随后的伴侣过表达不会阻止组装蛋白质聚集体。在某些位置的蛋白质沉积也构成了暂时灭活蛋白质的策略。Pyp1 就是这种情况，它是应激反应激酶 Sty1 的主要磷酸酶。施加压力后，错误折叠的 Pyp1 被隔离到胞质蛋白病灶中，而细胞核处的活性 Sty1 开启转录反应。综上所述，