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PMID: 17908928 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p.

Genes & development ·Vol. 21 ·No. 19 ·2007-10-01 ·Pages 2410-21

Erjavec N, Larsson L, Grantham J, Nyström T

Abstract

The levels of oxidatively damaged, carbonylated, proteins increase with the replicative age of yeast mother cells. We show here that such carbonylated proteins are associated with Hsp104p-containing protein aggregates and that these aggregates, like oxidized proteins, are retained in the progenitor cell during cytokinesis by a Sir2p-dependent process. Deletion of HSP104 resulted in a breakdown of damage asymmetry, and overproduction of Hsp104p partially restored damage retention in sir2Delta cells, suggesting that functional chaperones associated with protein aggregates are required for the establishment of damage asymmetry and that these functions are limited in sir2Delta cells. In line with this, Hsp104p and several Hsp70s displayed elevated damaged in sir2Delta cells, and protein aggregates were rescued at a slower rate in this mutant. Moreover, overproduction of Hsp104p suppressed the accelerated aging of cells lacking Sir2p, and drugs inhibiting damage segregation further demonstrated that spatial quality control is required to rejuvenate the progeny.

MeSH Terms
Cytokinesis Gene Deletion Heat-Shock Proteins/genetics,metabolism Histone Deacetylases/genetics Mutation Oxidation-Reduction Oxidative Stress/drug effects Saccharomyces cerevisiae/genetics,growth & development,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics Sirtuin 2 Sirtuins/genetics
Chemicals
Heat-Shock Proteins Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae HsP104 protein, S cerevisiae SIR2 protein, S cerevisiae Sirtuin 2 Sirtuins Histone Deacetylases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Erjavec Nika
Department of Cell and Molecular Biology, Göteborg University, 413 90 Göteborg, Sweden.
Larsson Lisa
Grantham Julie
Nyström Thomas
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.439307
Published
2007-10-01
Pages
2410-21
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1993872
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.439307 PMC Full Text View journal details
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