title: Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p.
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.
authors.affiliation: Department of Cell and Molecular Biology, Göteborg University, 413 90 Göteborg, Sweden.
authors.forename: Nika
authors.initials: N
authors.lastname: Erjavec
authors.forename: Lisa
authors.initials: L
authors.lastname: Larsson
authors.forename: Julie
authors.initials: J
authors.lastname: Grantham
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
mesh_terms: D048749:Cytokinesis; D017353:Gene Deletion; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics*; D009154:Mutation; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics*; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C070972:HsP104 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases