Heat Stress-Induced Life Span Extension in Yeast

Shama, Silvian; Lai, Chi-Yung; Antoniazzi, Jill M.; Jiang, James J.; Jazwinski, S. Michal

doi:10.1006/excr.1998.4279

Cited by 125 publications

(77 citation statements)

References 51 publications

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“…2C and Table 2). Genes in the Ras/cAMP/PKA pathway (namely, IRA2 and PDE2) previously have been shown to be able to regulate the heat shock response and thereby the expression of Hsp104 (39). In agreement with this finding, we observed a reduction in Hsp104 expression following heat shock in ira2⌬ and pde2⌬ mutants.…”

Section: Resultssupporting

confidence: 90%

Ssd1 Is Required for Thermotolerance and Hsp104-Mediated Protein Disaggregation in Saccharomyces cerevisiae

Mir

Fiedler

Cashikar

2009

Molecular and Cellular Biology

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In the budding yeast Saccharomyces cerevisiae, the Hsp104-mediated disaggregation of protein aggregates is essential for thermotolerance and to facilitate the maintenance of prions. In humans, protein aggregation is associated with neuronal death and dysfunction in many neurodegenerative diseases. Mechanisms of aggregation surveillance that regulate protein disaggregation are likely to play a major role in cell survival after acute stress. However, such mechanisms have not been studied. In a screen using the yeast gene deletion library for mutants unable to survive an aggregation-inducing heat stress, we find that SSD1 is required for Hsp104-mediated protein disaggregation. SSD1 is a polymorphic gene that plays a role in cellular integrity, longevity, and pathogenicity in yeast. Allelic variants of SSD1 regulate the level of thermotolerance and cell wall remodeling. We have shown that Ssd1 influences the ability of Hsp104 to hexamerize, to interact with the cochaperone Sti1, and to bind protein aggregates. These results provide a paradigm for linking Ssd1-mediated cellular integrity and Hsp104-mediated disaggregation to ensure the survival of cells with fewer aggregates.

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Section: Resultssupporting

confidence: 90%

Ssd1 Is Required for Thermotolerance and Hsp104-Mediated Protein Disaggregation in Saccharomyces cerevisiae

Mir

Fiedler

Cashikar

2009

Molecular and Cellular Biology

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“…For example, MMS induces double-strand DNA breaks, and the Sir proteins have been implicated in double-strand break repair (38,42,43,45). Similarly, a transient heat shock or high osmolarity have been shown to extend yeast cell life span (31,57), and Sir2 is required for longevity (32).…”

Section: Pnc1 As a Central Regulator Of The Sir2 Deacetylase Familymentioning

confidence: 99%

“…sion of life span in yeast caused by certain types of stress (31,57). Like Sir2 and Npt1 (8,52,54), Pnc1 is also phylogenetically conserved, with homologs identified in Eubacteria, Archaea, Drosophila, and Caenorhabditis elegans (22).…”

Section: Pnc1 As a Central Regulator Of The Sir2 Deacetylase Familymentioning

confidence: 99%

Nicotinamide Clearance by Pnc1 Directly Regulates Sir2-Mediated Silencing and Longevity

Gallo

Smith

2004

Molecular and Cellular Biology

179

182

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The Saccharomyces cerevisiae Sir2 protein is an NAD ؉ -dependent histone deacetylase (HDAC) that functions in transcriptional silencing and longevity. The NAD ؉ salvage pathway protein, Npt1, regulates Sir2-mediated processes by maintaining a sufficiently high intracellular NAD ؉ concentration. However, another NAD ؉ salvage pathway component, Pnc1, modulates silencing independently of the NAD ؉ concentration. Nicotinamide (NAM) is a by-product of the Sir2 deacetylase reaction and is a natural Sir2 inhibitor. Pnc1 is a nicotinamidase that converts NAM to nicotinic acid. Here we show that recombinant Pnc1 stimulates Sir2 HDAC activity in vitro by preventing the accumulation of NAM produced by Sir2. In vivo, telomeric, rDNA, and HM silencing are differentially sensitive to inhibition by NAM. Furthermore, PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, life span, and Hst1-mediated transcriptional repression. Finally, we show that stress suppresses the inhibitory effect of NAM through the induction of PNC1 expression. Pnc1, therefore, positively regulates Sir2-mediated silencing and longevity by preventing the accumulation of intracellular NAM during times of stress.

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“…These include low glucose concentration, low amino acid concentrations, heat stress, and osmotic stress (3,173,195). Consistent with the involvement of the PKA pathway in regulating life span, Pnc1 levels are increased in a cdc25 mutant strain as well (3).…”

Section: Regulation By Nicotinamide (I) Inhibition Of Sir2 By Nicotimentioning

confidence: 99%

Longevity Regulation inSaccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin

Bitterman

Medvedik

Sinclair

2003

Microbiol Mol Biol Rev

212

152

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When it was first proposed that the budding yeast Saccharomyces cerevisiae might serve as a model for human aging in 1959, the suggestion was met with considerable skepticism. Although yeast had proved a valuable model for understanding basic cellular processes in humans, it was difficult to accept that such a simple unicellular organism could provide information about human aging, one of the most complex of biological phenomena. While it is true that causes of aging are likely to be multifarious, there is a growing realization that all eukaryotes possess surprisingly conserved longevity pathways that govern the pace of aging. This realization has come, in part, from studies of S. cerevisiae, which has emerged as a highly informative and respected model for the study of life span regulation. Genomic instability has been identified as a major cause of aging, and over a dozen longevity genes have now been identified that suppress it. Here we present the key discoveries in the yeast-aging field, regarding both the replicative and chronological measures of life span in this organism. We discuss the implications of these findings not only for mammalian longevity but also for other key aspects of cell biology, including cell survival, the relationship between chromatin structure and genome stability, and the effect of internal and external environments on cellular defense pathways. We focus on the regulation of replicative life span, since recent findings have shed considerable light on the mechanisms controlling this process. We also present the specific methods used to study aging and longevity regulation in S. cerevisiae

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Heat Stress-Induced Life Span Extension in Yeast

Cited by 125 publications

References 51 publications

Ssd1 Is Required for Thermotolerance and Hsp104-Mediated Protein Disaggregation in Saccharomyces cerevisiae

Ssd1 Is Required for Thermotolerance and Hsp104-Mediated Protein Disaggregation in Saccharomyces cerevisiae

Nicotinamide Clearance by Pnc1 Directly Regulates Sir2-Mediated Silencing and Longevity

Longevity Regulation inSaccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin

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