Cargando…

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, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular r...

Descripción completa

Detalles Bibliográficos
Autores principales: Andersson, Rebecca, Eisele-Bürger, Anna Maria, Hanzén, Sarah, Vielfort, Katarina, Öling, David, Eisele, Frederik, Johansson, Gustav, Gustafsson, Tobias, Kvint, Kristian, Nyström, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822560/
https://www.ncbi.nlm.nih.gov/pubmed/33428620
http://dx.doi.org/10.1371/journal.pgen.1008951
_version_ 1783639668443578368
author Andersson, Rebecca
Eisele-Bürger, Anna Maria
Hanzén, Sarah
Vielfort, Katarina
Öling, David
Eisele, Frederik
Johansson, Gustav
Gustafsson, Tobias
Kvint, Kristian
Nyström, Thomas
author_facet Andersson, Rebecca
Eisele-Bürger, Anna Maria
Hanzén, Sarah
Vielfort, Katarina
Öling, David
Eisele, Frederik
Johansson, Gustav
Gustafsson, Tobias
Kvint, Kristian
Nyström, Thomas
author_sort Andersson, Rebecca
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7822560
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-78225602021-02-01 Differential role of cytosolic Hsp70s in longevity assurance and protein quality control Andersson, Rebecca Eisele-Bürger, Anna Maria Hanzén, Sarah Vielfort, Katarina Öling, David Eisele, Frederik Johansson, Gustav Gustafsson, Tobias Kvint, Kristian Nyström, Thomas PLoS Genet Research Article 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. Public Library of Science 2021-01-11 /pmc/articles/PMC7822560/ /pubmed/33428620 http://dx.doi.org/10.1371/journal.pgen.1008951 Text en © 2021 Andersson et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Andersson, Rebecca
Eisele-Bürger, Anna Maria
Hanzén, Sarah
Vielfort, Katarina
Öling, David
Eisele, Frederik
Johansson, Gustav
Gustafsson, Tobias
Kvint, Kristian
Nyström, Thomas
Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
title Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
title_full Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
title_fullStr Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
title_full_unstemmed Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
title_short Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
title_sort differential role of cytosolic hsp70s in longevity assurance and protein quality control
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822560/
https://www.ncbi.nlm.nih.gov/pubmed/33428620
http://dx.doi.org/10.1371/journal.pgen.1008951
work_keys_str_mv AT anderssonrebecca differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT eiseleburgerannamaria differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT hanzensarah differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT vielfortkatarina differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT olingdavid differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT eiselefrederik differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT johanssongustav differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT gustafssontobias differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT kvintkristian differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol
AT nystromthomas differentialroleofcytosolichsp70sinlongevityassuranceandproteinqualitycontrol