The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae
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Media type:
E-Article
Title:
The Pep4p vacuolar proteinase contributes to the turnover of oxidized proteins but PEP4 overexpression is not sufficient to increase chronological lifespan in Saccharomyces cerevisiae
Published in:
Microbiology, 152 (2006) 12, Seite 3595-3605
Language:
English
DOI:
10.1099/mic.0.29040-0
ISSN:
1465-2080;
1350-0872
Origination:
Footnote:
Description:
<jats:p>Turnover of damaged molecules is considered to play a key role in housekeeping of cells exposed to oxidative stress, and during the progress of ageing. In this work, global changes in the transcriptome were analysed during recovery of yeast cells after H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>stress. Regarding induced genes, those associated with protein fate were the most significantly over-represented. In addition to genes encoding subunits of the 20S proteasome, genes related to vacuolar proteolysis (<jats:italic>PEP4</jats:italic>and<jats:italic>LAP4</jats:italic>), protein sorting into the vacuole, and vacuolar fusion were found to be induced. The upregulation of<jats:italic>PEP4</jats:italic>gene expression was associated with an increase in Pep4p activity. The induction of genes related to proteolysis was correlated with an increased protein turnover after H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-induced oxidation. Furthermore, protein degradation and the removal of oxidized proteins decreased in Pep4p-deficient cells. Pep4p activity also increased during chronological ageing, and cells lacking Pep4p displayed a shortened lifespan associated with higher levels of carbonylated proteins.<jats:italic>PEP4</jats:italic>overexpression prevented the accumulation of oxidized proteins, but did not increase lifespan. These results indicate that Pep4p is important for protein turnover after oxidative damage; however, increased removal of oxidized proteins is not sufficient to enhance lifespan.</jats:p>