Spatial sequestration of misfolded proteins as an active chaperone-mediated process during heat stress

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