Differential role of cytosolic Hsp70s in longevity assurance and protein quality control

70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70’s in yeast, Ssa1-4, thought to be functionally redundant but absence Ssa1 Ssa2 causes a severe reduction reproduction accelerates replicative aging. In our efforts identify which Hsp70 activities most important longevity assurance, we systematically investigated capacity Ssa4 carry out different performed by Ssa1/2 overproducing cells lacking these chaperones. We found that Ssa4, when overproduced Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition aggregates into inclusions, promoted degradation. contrast, overproduction deficient failed restore recruitment disaggregase Hsp104 misfolded/aggregated proteins, fully clearance aggregates, bring back formation nucleolus-associated aggregation compartment. Exchanging nucleotide-binding domain with suppressed this ‘defect’ Ssa4. Interestingly, extended short lifespan ssa1 ? ssa2 mutant comparable to, or even longer than, wild type cells, demonstrating Hsp104-dependent is not prerequisite assurance yeast.