Proteasome synthesis and assembly are required for survival during stationary phase.
We examined the alterations in 20S proteasome homeostasis, protein oxidation, and cell viability that occur during the stationary phase or chronological model of yeast aging. Data in this report demonstrate that proteasome subunit expression is increased, proteasome composition is altered, and levels of individual proteasome proteolytic activities are elevated during stationary phase-induced aging in Saccharomyces cerevisiae. Despite such alterations, a progressive loss of proteasome-mediated protein degradation and a significant increase in protein oxidation were observed in cells maintained under stationary phase conditions. Deletion of UMP1, a gene necessary for 20S proteasome biogenesis, had no effect on cellular viability under normal growth conditions, but impaired the ability of cells to survive under stationary phase conditions. During stationary phase, the levels of oxidized protein increased more rapidly and to higher levels in the mutant lacking UMP1 than in the wild-type cells. Taken together, these data implicate a role for proteasome synthesis and altered 20S proteasome composition in maintaining viability during stationary phase, and demonstrate that even with these modifications a gradual loss of proteasome-mediated protein degradation occurs during stationary phase-induced aging. These data also suggest a role for impaired proteasome-mediated protein degradation in increased protein oxidation and cell death observed during the aging of eukaryotic cells.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
Qinghua
Q
Chen
Jeffrey
J
Thorpe
Qunxing
Q
Ding
Ismail S
IS
El-Amouri
Jeffrey N
JN
Keller
D000375:Aging; D002470:Cell Survival; D002918:Chymotrypsin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005609:Free Radicals; D017353:Gene Deletion; D018832:Molecular Chaperones / Q000235:genetics; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013997:Time Factors
D005609:Free Radicals; D018832:Molecular Chaperones; C110856:proteasome maturation protein; D002918:Chymotrypsin; D046988:Proteasome Endopeptidase Complex; D010100:Oxygen