In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 1 ( 2021-1-11), p. e1008951-
Abstract:
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 ssa1 Δ ssa2 Δ 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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1008951
DOI:
10.1371/journal.pgen.1008951.g001
DOI:
10.1371/journal.pgen.1008951.g002
DOI:
10.1371/journal.pgen.1008951.g003
DOI:
10.1371/journal.pgen.1008951.g004
DOI:
10.1371/journal.pgen.1008951.g005
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10.1371/journal.pgen.1008951.g006
DOI:
10.1371/journal.pgen.1008951.s001
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10.1371/journal.pgen.1008951.s002
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10.1371/journal.pgen.1008951.s003
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10.1371/journal.pgen.1008951.s004
DOI:
10.1371/journal.pgen.1008951.s005
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10.1371/journal.pgen.1008951.s006
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10.1371/journal.pgen.1008951.s007
DOI:
10.1371/journal.pgen.1008951.s008
DOI:
10.1371/journal.pgen.1008951.s009
DOI:
10.1371/journal.pgen.1008951.s010
DOI:
10.1371/journal.pgen.1008951.s011
DOI:
10.1371/journal.pgen.1008951.s012
DOI:
10.1371/journal.pgen.1008951.s013
DOI:
10.1371/journal.pgen.1008951.s014
DOI:
10.1371/journal.pgen.1008951.s015
DOI:
10.1371/journal.pgen.1008951.s016
DOI:
10.1371/journal.pgen.1008951.s017
DOI:
10.1371/journal.pgen.1008951.s018
DOI:
10.1371/journal.pgen.1008951.s019
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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