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

Autor: Andersson R; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Eisele-Bürger AM; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden., Hanzén S; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Vielfort K; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Öling D; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden., Eisele F; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden., Johansson G; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden., Gustafsson T; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden., Kvint K; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden., Nyström T; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Gothenburg, Sweden.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2021 Jan 11; Vol. 17 (1), pp. e1008951. Date of Electronic Publication: 2021 Jan 11 (Print Publication: 2021).
DOI: 10.1371/journal.pgen.1008951
Abstrakt: 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, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1Δ ssa2Δ mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast.
Competing Interests: The authors of this manuscript have read the journal’s policy and state the following competing interests: D.Ö. and F.E. are employed by AstraZeneca Mölndal, Sweden; S.H. is employed by Cochlear Nordic AB, Mölnlycke, Sweden.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje