title: Deletion of the mitochondrial Pim1/Lon protease in yeast results in accelerated aging and impairment of the proteasome.
abstract: The Saccharomyces cerevisiae homolog of the ATP-dependent Lon protease, Pim1p, is essential for mitochondrial protein quality control, DNA maintenance, and respiration. Here, we demonstrate that Pim1p activity declines in aging cells and that Pim1p deficiency shortens the replicative life span of yeast mother cells. This accelerated aging of pim1Δ cells is accompanied by elevated cytosolic levels of oxidized and aggregated proteins, as well as reduced proteasome activity. Overproduction of Hsp104p greatly diminishes aggregation of oxidized cytosolic proteins, rescues proteasome activity, and restores life span of pim1Δ cells to near wild-type levels. Our results show that defects in mitochondrial protein quality control have global intracellular effects leading to the increased generation of misfolded proteins and cytosolic protein aggregates, which are linked to a decline in replicative potential.
authors.affiliation: Department of Cell and Molecular Biology, Gothenburg University, Göteborg 41390, Sweden.
authors.forename: Nika
authors.initials: N
authors.lastname: Erjavec
authors.forename: Aurélien
authors.initials: A
authors.lastname: Bayot
authors.forename: Monique
authors.initials: M
authors.lastname: Gareil
authors.forename: Nadine
authors.initials: N
authors.lastname: Camougrand
authors.forename: Thomas
authors.initials: T
authors.lastname: Nystrom
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bulteau
mesh_terms: D049069:ATP-Dependent Proteases / Q000235:genetics*; D017353:Gene Deletion; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D013997:Time Factors
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D049069:ATP-Dependent Proteases; C085155:PIM1 protein, S cerevisiae; D012697:Serine Endopeptidases; D046988:Proteasome Endopeptidase Complex