Deteriorated stress response in stationary-phase yeast: Sir2 and Yap1 are essential for Hsf1 activation by heat shock and oxidative stress, respectively

• Published in: PloS one Vol. 9; no. 10; p. e111505
• Main Authors: Nussbaum, Inbal, Weindling, Esther, Jubran, Ritta, Cohen, Aviv, Bar-Nun, Shoshana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.10.2014; Public Library of Science (PLoS)
• Subjects: Activation; Aging; Baking yeast; Biochemistry; Biological evolution; Biology and Life Sciences; Cellular stress response; DNA-Binding Proteins - metabolism; Gene expression; Genetic engineering; Genetics; Glucose; Glucose - pharmacology; Heat shock; Heat-Shock Proteins - metabolism; Heat-Shock Response - drug effects; HSF1 protein; Kinases; Life sciences; Metabolism; Models, Biological; Molecular biology; NAD; NAD - metabolism; Oxidative stress; Oxidative Stress - drug effects; Phase transitions; Phosphorylation; Precursors; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Signaling; Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism; Sirtuin 2 - metabolism; Stress response; Transcription factors; Transcription Factors - metabolism; Trends; Yeast; Yes-associated protein; Tel Aviv Israel; Israel
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111505

Stationary-phase cultures have been used as an important model of aging, a complex process involving multiple pathways and signaling networks. However, the molecular processes underlying stress response of non-dividing cells are poorly understood, although deteriorated stress response is one of the hallmarks of aging. The budding yeast Saccharomyces cerevisiae is a valuable model organism to study the genetics of aging, because yeast ages within days and are amenable to genetic manipulations. As a unicellular organism, yeast has evolved robust systems to respond to environmental challenges. This response is orchestrated largely by the conserved transcription factor Hsf1, which in S. cerevisiae regulates expression of multiple genes in response to diverse stresses. Here we demonstrate that Hsf1 response to heat shock and oxidative stress deteriorates during yeast transition from exponential growth to stationary-phase, whereas Hsf1 activation by glucose starvation is maintained. Overexpressing Hsf1 does not significantly improve heat shock response, indicating that Hsf1 dwindling is not the major cause for Hsf1 attenuated response in stationary-phase yeast. Rather, factors that participate in Hsf1 activation appear to be compromised. We uncover two factors, Yap1 and Sir2, which discretely function in Hsf1 activation by oxidative stress and heat shock. In Δyap1 mutant, Hsf1 does not respond to oxidative stress, while in Δsir2 mutant, Hsf1 does not respond to heat shock. Moreover, excess Sir2 mimics the heat shock response. This role of the NAD+-dependent Sir2 is supported by our finding that supplementing NAD+ precursors improves Hsf1 heat shock response in stationary-phase yeast, especially when combined with expression of excess Sir2. Finally, the combination of excess Hsf1, excess Sir2 and NAD+ precursors rejuvenates the heat shock response.