Abstract
Silent Information Regulator 2 (Sir2), a conserved NAD+-dependent histone deacetylase, has been implicated as one of the key factors in regulating stress response and longevity. Here, we report that the role of Sir2 in oxidative stress resistance and chronological lifespan is dependent on growth phase in yeast. In exponential phase, sir2Δ cells were more resistant to H2O2 stress and had a longer chronological lifespan than wild type. By contrast, in post-diauxic phase, sir2Δ cells were less resistant to H2O2 stress and had a shorter chronological lifespan than wild type cells. Similarly, the expression of antioxidant genes, which are essential to cope with oxidative stress, was regulated by Sir2 in a growth phasedependent manner. Collectively, our findings highlight the importance of the metabolic state of the cell in determining whether Sir2 can protect against or accelerate cellular aging of yeast.
Similar content being viewed by others
References
Aguilaniu, H., Gustafsson, L., Rigoulet, M., and Nystrom, T. 2003. Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299, 1751–1753.
Beers, R.F., and Sizer, I.W. 1952. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 195, 133–140.
Bishop, N.A. and Guarente, L. 2007. Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nat. Rev. Genet. 8, 835–844.
Burtner, C.R., Murakami, C.J., Kennedy, B.K., and Kaeberlein, M. 2009. A molecular mechanism of chronological aging in yeast. Cell Cycle 8, 1256–1270.
DeRisi, J.L., Iyer, V.R., and Brown, P.O. 1997. Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278, 680–686.
Erjavec, N. and Nystrom, T. 2007. Sir2p-dependent protein segregation gives rise to a superior reactive oxygen species management in the progeny of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 104, 10877–10891.
Fabrizio, P., Gattazzo, C., Battistella, L., Wei, M., Cheng, C., Mc-Grew, K., and Longo, V.D. 2005. Sir2 blocks extreme life-span extension. Cell 123, 655–667.
Galdieri, L., Mehrotra, S., Yu, S., and Vancura, A. 2010. Transcriptional regulation in yeast during diauxic shift and stationary phase. Omics 14, 629–638.
Gottschling, D.E., Aparicio, O.M., Billington, B.L., and Zakian, V.A. 1990. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63, 751–762.
Gray, J.V., Petsko, G.A., Johnston, G.C., Ringe, D., Singer, R.A., and Werner-Washburne, M. 2004. “Sleeping beauty”: quiescence in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 68, 187–206.
Ivy, J.M., Klar, A.J., and Hicks, J.B. 1986. Cloning and characterization of four SIR genes of Saccharomyces cerevisiae. Mol. Cell. Biol. 6, 688–702.
Kaeberlein, M., Andalis, A.A., Fink, G.R., and Guarente, L. 2002. High osmolarity extends life span in Saccharomyces cerevisiae by a mechanism related to calorie restriction. Mol. Cell. Biol. 22, 8056–8066.
Kaeberlein, M., McVey, M., and Guarente, L. 1999. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13, 2570–2580.
Keogh, M.C., Mennella, T.A., Sawa, C., Berthelet, S., Krogan, N.J., Wolek, A., Podolny, V., Carpenter, L.R., Greenblatt, J.F., Baetz, K., and et al. 2006. The Saccharomyces cerevisiae histone H2A variant Htz1 is acetylated by NuA4. Genes Dev. 20, 660–665.
Laun, P., Pichova, A., Madeo, F., Fuchs, J., Ellinger, A., Kohlwein, S., Dawes, I., Frohlich, K.U., and Breitenbach, M. 2001. Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Mol. Microbiol. 39, 1166–1173.
Lin, S.J., Ford, E., Haigis, M., Liszt, G., and Guarente, L. 2004. Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 18, 12–16.
Liu, B., Larsson, L., Caballero, A., Hao, X., Oling, D., Grantham, J., and Nystrom, T. 2010. The polarisome is required for segregation and retrograde transport of protein aggregates. Cell 140, 257–267.
Longo, V.D. and Fabrizio, P. 2012. Chronological aging in Saccharomyces cerevisiae. Subcell Biochem. 57, 101–121.
Longo, V.D., Gralla, E.B., and Valentine, J.S. 1996. Superoxide dismutase activity is essential for stationary phase survival in Saccharomyces cerevisiae. Mitochondrial production of toxic oxygen species in vivo. J. Biol. Chem. 271, 12275–12280.
Longo, V.D., Shadel, G.S., Kaeberlein, M., and Kennedy, B. 2012. Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metab. 16, 18–31.
Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., and Kroemer, G. 2013. The hallmarks of aging. Cell 153, 1194–1217.
Medvedik, O., Lamming, D.W., Kim, K.D., and Sinclair, D.A. 2007. MSN2 and MSN4 link calorie restriction and TOR to sirtuinmediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol. 5, e271.
Merksamer, P.I., Liu, Y., He, W., Hirschey, M.D., Chen, D., and Verdin, E. 2013. The sirtuins, oxidative stress and aging: an emerging link. Aging (Albany NY) 5, 144–150.
Molin, M., Yang, J., Hanzen, S., Toledano, M.B., Labarre, J., and Nystrom, T. 2011. Life span extension and H2O2 resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae. Mol. Cell. 43, 823–833.
Morano, K.A., Grant, C.M., and Moye-Rowley, W.S. 2012. The response to heat shock and oxidative stress in Saccharomyces cerevisiae. Genetics 190, 1157–1195.
Mortimer, R.K. and Johnston, J.R. 1959. Life span of individual yeast cells. Nature 183, 1751–1752.
Murakami, C., Delaney, J.R., Chou, A., Carr, D., Schleit, J., Sutphin, G.L., An, E.H., Castanza, A.S., Fletcher, M., Goswami, S., and et al. 2012. pH neutralization protects against reduction in replicative lifespan following chronological aging in yeast. Cell. Cycle 11, 3087–3096.
Murakami, C.J., Burtner, C.R., Kennedy, B.K., and Kaeberlein, M. 2008. A method for high-throughput quantitative analysis of yeast chronological life span. J. Gerontol. A Biol. Sci. Med. Sci. 63, 113–121.
Pan, Y. 2011. Mitochondria, reactive oxygen species, and chronological aging: a message from yeast. Exp. Gerontol. 46, 847–852.
Reverter-Branchat, G., Cabiscol, E., Tamarit, J., and Ros, J. 2004. Oxidative damage to specific proteins in replicative and chronological-aged Saccharomyces cerevisiae: common targets and prevention by calorie restriction. J. Biol. Chem. 279, 31983–31989.
Rine, J. and Herskowitz, I. 1987. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics 116, 9–22.
Sinclair, D.A. and Guarente, L. 1997. Extrachromosomal rDNA circles-a cause of aging in yeast. Cell 91, 1033–1042.
Smith, D.L., McClure, J.M., Matecic, M., and Smith, J.S. 2007. Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins. Aging Cell 6, 649–662.
Vendrell, A., Martinez-Pastor, M., Gonzalez-Novo, A., Pascual-Ahuir, A., Sinclair, D.A., Proft, M., and Posas, F. 2011. Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase. EMBO Rep. 12, 1062–1068.
Werner-Washburne, M., Braun, E., Johnston, G.C., and Singer, R.A. 1993. Stationary phase in the yeast Saccharomyces cerevisiae. Microbiol. Rev. 57, 383–401.
Wierman, M.B. and Smith, J.S. 2013. Yeast sirtuins and the regulation of aging. FEMS Yeast Res. doi: 10.1111/1567-1364.12115.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kang, W.K., Kim, Y.H., Kim, BS. et al. Growth phase-dependent roles of Sir2 in oxidative stress resistance and chronological lifespan in yeast. J Microbiol. 52, 652–658 (2014). https://doi.org/10.1007/s12275-014-4173-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12275-014-4173-2