Yeast Aging and Apoptosis

  • Peter LaunEmail author
  • Sabrina Büttner
  • Mark Rinnerthaler
  • William C. Burhans
  • Michael Breitenbach
Part of the Subcellular Biochemistry book series (SCBI, volume 57)


A concerted balance between proliferation and apoptosis is essential to the survival of multicellular organisms. Thus, apoptosis per se, although it is a destructive process leading to the death of single cells, also serves as a pro-survival mechanism that ensures healthy organismal development and acts as a life-prolonging or anti-aging program. The discovery that yeast also possess a functional and, in many cases, highly conserved apoptotic machinery has made it possible to study the relationships between aging and apoptosis in depth using a well-established genetic system and the powerful tools available to yeast researchers for investigating complex physiological and cytological interactions. The aging process of yeast, be it replicative or chronological aging, is closely related to apoptosis, although it remains unclear whether apoptosis is a causal feature of the aging process or vice versa. Nevertheless, experimental results obtained during the past several years clearly demonstrate that yeast serve as a powerful and versatile experimental system for understanding the interconnections between these two fundamentally important cellular and physiological pathways.


Apoptosis Necrosis Replicative aging Chronological aging Cell death 



We are grateful to the Austrian Science Fund FWF (Vienna, Austria) for grants S9302-B05 (to M.B.) and T414-B09 (to S.B.) and to the EC (Brussels, Europe) for project MIMAGE (contract no. 512020; to M.B.).


  1. Aguilaniu H, Gustafsson L, Rigoulet M, Nystrom T (2003) Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299:1751–1753PubMedGoogle Scholar
  2. Ahn SH, Henderson KA, Keeney S, Allis CD (2005) H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle 4:780–783PubMedGoogle Scholar
  3. Alderson MR, Tough TW, Davis-Smith T, Braddy S, Falk B, Schooley KA, Goodwin RG, Smith CA, Ramsdell F, Lynch DH (1995) Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med 181:71–77PubMedGoogle Scholar
  4. Allen C, Buttner S, Aragon AD, Thomas JA, Meirelles O, Jaetao JE, Benn D, Ruby SW, Veenhuis M, Madeo F et al (2006) Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures. J Cell Biol 174:89–100PubMedGoogle Scholar
  5. Arnheim G (1890) Coagulationsnekrose und Kernschwund. Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin 120:367–383Google Scholar
  6. Bandara PDS, Flattery-O’Brien JA, Grant CM, Dawes IW (1998) Involvement of the Saccharomyces cerevisiae UTH1 gene in the oxidative-stress response. Curr Genet 34:259–268PubMedGoogle Scholar
  7. Bettiga M, Calzari L, Orlandi I, Alberghina L, Vai M (2004) Involvement of the yeast metacaspase Yca1 in ubp10Delta-programmed cell death. FEMS Yeast Res 5:141–147PubMedGoogle Scholar
  8. Bink A, Govaert G, Francois IE, Pellens K, Meerpoel L, Borgers M, Van Minnebruggen G, Vroome V, Cammue BP, Thevissen K (2010) A fungicidal piperazine-1-carboxamidine induces mitochondrial fission-dependent apoptosis in yeast. FEMS Yeast Res 10:812–818PubMedGoogle Scholar
  9. Birnbaum MJ, Clem RJ, Miller LK (1994) An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. J Virol 68:2521–2528PubMedGoogle Scholar
  10. Bischoff JR, Casso D, Beach D (1992) Human p53 inhibits growth in Schizosaccharomyces pombe. Mol Cell Biol 12:1405–1411PubMedGoogle Scholar
  11. Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Kontgen F, Adams JM, Strasser A (1999) Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735–1738PubMedGoogle Scholar
  12. Braun RJ, Zischka H, Madeo F, Eisenberg T, Wissing S, Buttner S, Engelhardt SM, Buringer D, Ueffing M (2006) Crucial mitochondrial impairment upon CDC48 mutation in apoptotic yeast. J Biol Chem 281:25757–25767PubMedGoogle Scholar
  13. Breitenbach M, Madeo F, Laun P, Heeren G, Jarolim S, Fröhlich K-U, Wissing S, Pichova A (2003) Yeast as a model for ageing and apoptosis research. In: Model systems in aging, Springer, Heidelberg, pp 61–97Google Scholar
  14. Burhans WC, Weinberger M (2007) DNA replication stress, genome instability and aging. Nucleic Acids Res 35:7545–7556PubMedGoogle Scholar
  15. Burtner CR, Murakami CJ, Olsen B, Kennedy BK, Kaeberlein M (2011) A genomic analysis of chronological longevity factors in budding yeast. Cell Cycle 10:1385–1396PubMedGoogle Scholar
  16. Buttner S, Eisenberg T, Carmona-Gutierrez D, Ruli D, Knauer H, Ruckenstuhl C, Sigrist C, Wissing S, Kollroser M, Frohlich KU et al (2007) Endonuclease G regulates budding yeast life and death. Mol Cell 25:233–246PubMedGoogle Scholar
  17. Buttner S, Eisenberg T, Herker E, Carmona-Gutierrez D, Kroemer G, Madeo F (2006) Why yeast cells can undergo apoptosis: death in times of peace, love, and war. J Cell Biol 175:521–525PubMedGoogle Scholar
  18. Camougrand N, Grelaud-Coq A, Marza E, Priault M, Bessoule JJ, Manon S (2003) The product of the UTH1 gene, required for Bax-induced cell death in yeast, is involved in the response to rapamycin. Mol Microbiol 47:495–506PubMedGoogle Scholar
  19. Camougrand N, Kissova I, Velours G, Manon S (2004) Uth1p: a yeast mitochondrial protein at the crossroads of stress, degradation and cell death. FEMS Yeast Res 5:133–140PubMedGoogle Scholar
  20. Camougrand NM, Mouassite M, Velours GM, Guerin MG (2000) The “SUN” family: UTH1, an ageing gene, is also involved in the regulation of mitochondria biogenesis in Saccharomyces cerevisiae. Arch Biochem Biophys 375:154–160PubMedGoogle Scholar
  21. Carmona-Gutierrez D, Eisenberg T, Buttner S, Meisinger C, Kroemer G, Madeo F (2010) Apoptosis in yeast: triggers, pathways, subroutines. Cell Death Differ 17:763–773PubMedGoogle Scholar
  22. Chinnaiyan AM, O’Rourke K, Lane BR, Dixit VM (1997) Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 275:1122–1126PubMedGoogle Scholar
  23. Chiocchetti A, Zhou J, Zhu H, Karl T, Haubenreisser O, Rinnerthaler M, Heeren G, Oender K, Bauer J, Hintner H et al (2007) Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life span. Exp Gerontol 42:275–286PubMedGoogle Scholar
  24. Chiou SK, Rao L, White E (1994) Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol 14:2556–2563PubMedGoogle Scholar
  25. Cleary ML, Smith SD, Sklar J (1986) Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47:19–28PubMedGoogle Scholar
  26. Clem RJ, Fechheimer M, Miller LK (1991) Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 254:1388–1390PubMedGoogle Scholar
  27. Conradt B, Xue D (2005) Programmed cell death. WormBook 1–13Google Scholar
  28. Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, Dahl HH, Chinnery PF (2008) A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet 40:249–254PubMedGoogle Scholar
  29. Cvetanovic M, Mitchell JE, Patel V, Avner BS, Su Y, van der Saag PT, Witte PL, Fiore S, Levine JS, Ucker DS (2006) Specific recognition of apoptotic cells reveals a ubiquitous and unconventional innate immunity. J Biol Chem 281:20055–20067PubMedGoogle Scholar
  30. De Felici M, Lobascio AM, Klinger FG (2007) Cell death in fetal oocytes: Many players for multiple pathways. Autophagy 4:240–242PubMedGoogle Scholar
  31. Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44:817–829PubMedGoogle Scholar
  32. Erjavec N, Larsson L, Grantham J, Nystrom T (2007) Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p. Genes Dev 21:2410–2421PubMedGoogle Scholar
  33. Erjavec N, 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 104:10877–10881PubMedGoogle Scholar
  34. Evans CJ, Aguilera RJ (2003) DNase II: genes, enzymes and function. Gene 322:1–15PubMedGoogle Scholar
  35. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 148:2207–2216PubMedGoogle Scholar
  36. Fahrenkrog B, Sauder U, Aebi U (2004) The S. cerevisiae HtrA-like protein Nma111p is a nuclear serine protease that mediates yeast apoptosis. J Cell Sci 117:115–126PubMedGoogle Scholar
  37. Fannjiang Y, Cheng WC, Lee SJ, Qi B, Pevsner J, McCaffery JM, Hill RB, Basanez G, Hardwick JM (2004) Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev 18:2785–2797PubMedGoogle Scholar
  38. Fernandez-Teran MA, Hinchliffe JR, Ros MA (2006) Birth and death of cells in limb development: a mapping study. Dev Dyn 235:2521–2537PubMedGoogle Scholar
  39. Flemming W (1885) Uber die Bildung von Richtungsfiguren in Saugethiereiern beim Untergang Graaf’scher Follikel. Arch Anat EntwGesch 1885:221–224Google Scholar
  40. Francis BR, White KH, Thorsness PE (2007) Mutations in the Atp1p and Atp3p subunits of yeast ATP synthase differentially affect respiration and fermentation in Saccharomyces cerevisiae. J Bioenerg Biomembr 39:127–144PubMedGoogle Scholar
  41. Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ (2001) The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 1:515–525PubMedGoogle Scholar
  42. Glücksmann A (1951) Cell deaths in normal vertebrate ontogeny. Biol Rev Camb Philos Soc 26:59–86Google Scholar
  43. Granot D, Levine A, Dor-Hefetz E (2003) Sugar-induced apoptosis in yeast cells. FEMS Yeast Res 4:7–13PubMedGoogle Scholar
  44. Guaragnella N, Bobba A, Passarella S, Marra E, Giannattasio S (2010) Yeast acetic acid-induced programmed cell death can occur without cytochrome c release which requires metacaspase YCA1. FEBS Lett 584:224–228PubMedGoogle Scholar
  45. Halliwell B, Gutteridge J (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, New YorkGoogle Scholar
  46. Hamon Y, Chambenoit O, Chimini G (2002) ABCA1 and the engulfment of apoptotic cells. Biochim Biophys Acta 1585:64–71PubMedGoogle Scholar
  47. Hampel B, Malisan F, Niederegger H, Testi R, Jansen-Durr P (2004) Differential regulation of apoptotic cell death in senescent human cells. Exp Gerontol 39:1713–1721PubMedGoogle Scholar
  48. Hauptmann P, Riel C, Kunz-Schughart LA, Frohlich KU, Madeo F, Lehle L (2006) Defects in N-glycosylation induce apoptosis in yeast. Mol Microbiol 59:765–778PubMedGoogle Scholar
  49. He H, Sun Y (2007) Ribosomal protein S27L is a direct p53 target that regulates apoptosis. Oncogene 26:2707–2716PubMedGoogle Scholar
  50. Heath-Engel HM, Shore GC (2006) Mitochondrial membrane dynamics, cristae remodelling and apoptosis. Biochim Biophys Acta 1763:549–560PubMedGoogle Scholar
  51. Hedgecock EM, Sulston JE, Thomson JN (1983) Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science 220:1277–1279PubMedGoogle Scholar
  52. Heeren G, Rinnerthaler M, Laun P, von Seyerl P, Kossler S, Klinger H, Hager M, Bogengruber E, Jarolim S, Simon-Nobbe B et al (2009) The mitochondrial ribosomal protein of the large subunit, Afo1p, determines cellular longevity through mitochondrial back-signaling via TOR1. Aging (Albany NY) 1:622–636Google Scholar
  53. Hengartner MO (1997) Genetic control of programmed cell death and aging in the nematode Caenorhabditis elegans. Exp Gerontol 32:363–374PubMedGoogle Scholar
  54. Henson PM, Hume DA (2006) Apoptotic cell removal in development and tissue homeostasis. Trends Immunol 27:244–250PubMedGoogle Scholar
  55. Herker E, Jungwirth H, Lehmann KA, Maldener C, Frohlich KU, Wissing S, Buttner S, Fehr M, Sigrist S, Madeo F (2004) Chronological aging leads to apoptosis in yeast. J Cell Biol 164:501–507PubMedGoogle Scholar
  56. Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318–327PubMedGoogle Scholar
  57. Horvitz HR, Ellis HM, Stemberg PW (1982) Programmed cell death in nematode development. Neurosci Comment 1:56–65Google Scholar
  58. Huh GH, Damsz B, Matsumoto TK, Reddy MP, Rus AM, Ibeas JI, Narasimhan ML, Bressan RA, Hasegawa PM (2002) Salt causes ion disequilibrium-induced programmed cell death in yeast and plants. Plant J 29:649–659PubMedGoogle Scholar
  59. Jacoby M (1900) Uber die fermentative Eiweissspaltung und Ammoniakbildung in der Leber. Hoppe-Seyler’s Z Physiol Chem 30:149–159Google Scholar
  60. Jacotot E, Ferri KF, Kroemer G (2000) Apoptosis and cell cycle: distinct checkpoints with overlapping upstream control. Pathol Biol (Paris) 48:271–279Google Scholar
  61. Jazwinski SM, Egilmez NK, Chen JB (1989) Replication control and cellular life span. Exp Gerontol 24:423–436PubMedGoogle Scholar
  62. Jurgensmeier JM, Krajewski S, Armstrong RC, Wilson GM, Oltersdorf T, Fritz LC, Reed JC, Ottilie S (1997) Bax- and Bak-induced cell death in the fission yeast Schizosaccharomyces pombe. Mol Biol Cell 8:325–339PubMedGoogle Scholar
  63. Karbowski M, Lee YJ, Gaume B, Jeong SY, Frank S, Nechushtan A, Santel A, Fuller M, Smith CL, Youle RJ (2002) Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J Cell Biol 159:931–938PubMedGoogle Scholar
  64. Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y, Nagata S (2001) Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science 292:1546–1549PubMedGoogle Scholar
  65. Kawane K, Fukuyama H, Yoshida H, Nagase H, Ohsawa Y, Uchiyama Y, Okada K, Iida T, Nagata S (2003) Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation. Nat Immunol 4:138–144PubMedGoogle Scholar
  66. Kennedy BK, Austriaco NR, Zhang JS, Guarente L (1995) Mutation in the silencing gene Sir4 can delay aging in Saccharomyces cerevisiae. Cell 80:485–496PubMedGoogle Scholar
  67. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedGoogle Scholar
  68. Kirkwood TB, Proctor CJ (2003) Somatic mutations and ageing in silico. Mech Ageing Dev 124:85–92PubMedGoogle Scholar
  69. Klebs E (1889) Die Allgemeine Pathologie. Zweiter Theil. Störungen des Baues und der Zusammensetzung. Verlag Gustav Fischer, JenaGoogle Scholar
  70. Klinger H, Rinnerthaler M, Lam YT, Laun P, Heeren G, Klocker A, Simon-Nobbe B, Dickinson JR, Dawes IW, Breitenbach M (2010) Quantitation of (a)symmetric inheritance of functional and of oxidatively damaged mitochondrial aconitase in the cell division of old yeast mother cells. Exp Gerontol 45:533–542PubMedGoogle Scholar
  71. Krause KH (2007) Aging: a revisited theory based on free radicals generated by NOX family NADPH oxidases. Exp Gerontol 42:256–262PubMedGoogle Scholar
  72. Krieser RJ, White K (2002) Engulfment mechanism of apoptotic cells. Curr Opin Cell Biol 14:734–738PubMedGoogle Scholar
  73. Lackner LL, Nunnari JM (2009) The molecular mechanism and cellular functions of mitochondrial division. Biochim Biophys Acta 1792:1138–1144PubMedGoogle Scholar
  74. Laun P, Heeren G, Rinnerthaler M, Rid R, Kossler S, Koller L, Breitenbach M (2008) Senescence and apoptosis in yeast mother cell-specific aging and in higher cells: a short review. Biochim Biophys Acta 1783:1328–1334PubMedGoogle Scholar
  75. Laun P, Pichova A, Madeo F, Fuchs J, Ellinger A, Kohlwein S, Dawes I, Frohlich KU, Breitenbach M (2001) Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Mol Microbiol 39:1166–1173PubMedGoogle Scholar
  76. Laun P, Rinnerthaler M, Bogengruber E, Heeren G, Breitenbach M (2006) Yeast as a model for chronological and reproductive aging – a comparison. Exp Gerontol 41:1208–1212PubMedGoogle Scholar
  77. Lee RE, Brunette S, Puente LG, Megeney LA (2010) Metacaspase Yca1 is required for clearance of insoluble protein aggregates. Proc Natl Acad Sci USA 107:13348–13353PubMedGoogle Scholar
  78. Leonhard K, Stiegler A, Neupert W, Langer T (1999) Chaperone-like activity of the AAA domain of the yeast Yme1 AAA protease. Nature 398:348–351PubMedGoogle Scholar
  79. Lettre G, Hengartner MO (2006) Developmental apoptosis in C. elegans: a complex CEDnario. Nat Rev Mol Cell Biol 7:97–108PubMedGoogle Scholar
  80. Li W, Sun L, Liang Q, Wang J, Mo W, Zhou B (2006) Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging. Mol Biol Cell 17:1802–1811PubMedGoogle Scholar
  81. Ligr M, Velten I, Frohlich E, Madeo F, Ledig M, Frohlich KU, Wolf DH, Hilt W (2001) The proteasomal substrate Stm1 participates in apoptosis-like cell death in yeast. Mol Biol Cell 12:2422–2432PubMedGoogle Scholar
  82. Lithgow GJ, Kirkwood TB (1996) Mechanisms and evolution of aging. Science 273:80PubMedGoogle Scholar
  83. Liu B, Larsson L, Caballero A, Hao X, Oling D, Grantham J, Nystrom T (2010) The polarisome is required for segregation and retrograde transport of protein aggregates. Cell 140:257–267PubMedGoogle Scholar
  84. Liu H, Peng HW, Cheng YS, Yuan HS, Yang-Yen HF (2005) Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP. Mol Cell Biol 25:3117–3126PubMedGoogle Scholar
  85. Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157PubMedGoogle Scholar
  86. Longo VD, Mitteldorf J, Skulachev VP (2005) Programmed and altruistic ageing. Nat Rev Genet 6:866–872PubMedGoogle Scholar
  87. Ludovico P, Rodrigues F, Almeida A, Silva MT, Barrientos A, Corte-Real M (2002) Cytochrome c release and mitochondria involvement in programmed cell death induced by acetic acid in Saccharomyces cerevisiae. Mol Biol Cell 13:2598–2606PubMedGoogle Scholar
  88. Ludovico P, Sousa MJ, Silva MT, Leao C, Corte-Real M (2001) Saccharomyces cerevisiae commits to a programmed cell death process in response to acetic acid. Microbiology 147:2409–2415PubMedGoogle Scholar
  89. Luo Y, Rockow-Magnone SK, Kroeger PE, Frost L, Chen Z, Han EK, Ng SC, Simmer RL, Giranda VL (2001) Blocking Chk1 expression induces apoptosis and abrogates the G2 checkpoint mechanism. Neoplasia 3:411–419PubMedGoogle Scholar
  90. Madeo F, Frohlich E, Frohlich KU (1997) A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 139:729–734PubMedGoogle Scholar
  91. Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH, Frohlich KU (1999) Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 145:757–767PubMedGoogle Scholar
  92. Madeo F, Herker E, Maldener C, Wissing S, Lachelt S, Herlan M, Fehr M, Lauber K, Sigrist SJ, Wesselborg S et al (2002) A caspase-related protease regulates apoptosis in yeast. Mol Cell 9:911–917PubMedGoogle Scholar
  93. Managbanag JR, Witten TM, Bonchev D, Fox LA, Tsuchiya M, Kennedy BK, Kaeberlein M (2008) Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity. PLoS ONE 3(11):e3802. doi:10.1371/journal.pone.0003802Google Scholar
  94. Manon S, Chaudhuri B, Guerin M (1997) Release of cytochrome c and decrease of cytochrome c oxidase in Bax-expressing yeast cells, and prevention of these effects by coexpression of Bcl-xL. FEBS Lett 415:29–32PubMedGoogle Scholar
  95. Manon S, Priault M, Camougrand N (2001) Mitochondrial AAA-type protease Yme1p is involved in Bax effects on cytochrome c oxidase. Biochem Biophys Res Commun 289:1314–1319PubMedGoogle Scholar
  96. Marchetti MA, Weinberger M, Murakami Y, Burhans WC, Huberman JA (2006) Production of reactive oxygen species in response to replication stress and inappropriate mitosis in fission yeast. J Cell Sci 119:124–131PubMedGoogle Scholar
  97. Mazzoni C, Palermo V, Torella M, Falcone C (2005) HIR1, the co-repressor of histone gene transcription of Saccharomyces cerevisiae, acts as a multicopy suppressor of the apoptotic phenotypes of the LSM4 mRNA degradation mutant. FEMS Yeast Res 5:1229–1235PubMedGoogle Scholar
  98. Medawar PB (1951) Inaugural lecture: an unsolved problem of biology. HK Lewis & Co Ltd, London, p. 24Google Scholar
  99. Mitsui K, Nakagawa D, Nakamura M, Okamoto T, Tsurugi K (2005) Valproic acid induces apoptosis dependent of Yca1p at concentrations that mildly affect the proliferation of yeast. FEBS Lett 579:723–727PubMedGoogle Scholar
  100. Miura M, Zhu H, Rotello R, Hartwieg EA, Yuan J (1993) Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75:653–660PubMedGoogle Scholar
  101. Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL et al (1996) X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 381:335–341PubMedGoogle Scholar
  102. Narasimhan ML, Damsz B, Coca MA, Ibeas JI, Yun DJ, Pardo JM, Hasegawa PM, Bressan RA (2001) A plant defense response effector induces microbial apoptosis. Mol Cell 8:921–930PubMedGoogle Scholar
  103. Nargund AM, Avery SV, Houghton JE (2008) Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae. Apoptosis 13:811–821PubMedGoogle Scholar
  104. Naylor K, Ingerman E, Okreglak V, Marino M, Hinshaw JE, Nunnari J (2006) Mdv1 interacts with assembled dnm1 to promote mitochondrial division. J Biol Chem 281:2177–2183PubMedGoogle Scholar
  105. Nestelbacher R, Laun P, Breitenbach M (1999) Images in experimental gerontology. A senescent yeast mother cell. Exp Gerontol 34:895–896PubMedGoogle Scholar
  106. Nissen F (1886) Uber das Verhalten der Kerne in den Milchdrusenzellen bei der Absonderung. Arch Mikroskop Anat 26:337–342Google Scholar
  107. Nystrom T (2005) Role of oxidative carbonylation in protein quality control and senescence. EMBO J 24:1311–1317PubMedGoogle Scholar
  108. Oberst A, Bender C, Green DR (2008) Living with death: the evolution of the mitochondrial pathway of apoptosis in animals. Cell Death Differ 15:1139–1146PubMedGoogle Scholar
  109. Odorisio T, Rodriguez TA, Evans EP, Clarke AR, Burgoyne PS (1998) The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis. Nat Genet 18:257–261PubMedGoogle Scholar
  110. Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619PubMedGoogle Scholar
  111. Orgel LE (1963) The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc Natl Acad Sci USA 49:517–521PubMedGoogle Scholar
  112. Palermo V, Falcone C, Mazzoni C (2007) Apoptosis and aging in mitochondrial morphology mutants of S. cerevisiae. Folia Microbiol (Praha) 52:479–483Google Scholar
  113. Papa S, Skulachev VP (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174:305–319PubMedGoogle Scholar
  114. Pavlov EV, Priault M, Pietkiewicz D, Cheng EH, Antonsson B, Manon S, Korsmeyer SJ, Mannella CA, Kinnally KW (2001) A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast. J Cell Biol 155:725–731PubMedGoogle Scholar
  115. Pichova A, Vondrakova D, Breitenbach M (1997) Mutants in the Saccharomyces cerevisiae RAS2 gene influence life span, cytoskeleton, and regulation of mitosis. Can J Microbiol 43:774–781PubMedGoogle Scholar
  116. Pietenpol JA, Stewart ZA (2002) Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis. Toxicology 181–182:475–481PubMedGoogle Scholar
  117. Piper PW, Harris NL, MacLean M (2006) Preadaptation to efficient respiratory maintenance is essential both for maximal longevity and the retention of replicative potential in chronologically ageing yeast. Mech Ageing Dev 127:733–740PubMedGoogle Scholar
  118. Powers RW, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Gene Dev 20:174–184PubMedGoogle Scholar
  119. Pozniakovsky AI, Knorre DA, Markova OV, Hyman AA, Skulachev VP, Severin FF (2005a) Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. J Cell Biol 168:257–269PubMedGoogle Scholar
  120. Pozniakovsky AI, Knorre DA, Markova OV, Hyman AA, Skulachev VP, Severin FF (2005b) Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. J Cell Biol 168:257–269PubMedGoogle Scholar
  121. Qiu J, Yoon JH, Shen B (2005) Search for apoptotic nucleases in yeast: role of Tat-D nuclease in apoptotic DNA degradation. J Biol Chem 280:15370–15379PubMedGoogle Scholar
  122. Requena JR, Levine RL, Stadtman ER (2003) Recent advances in the analysis of oxidized proteins. Amino Acids 25:221–226PubMedGoogle Scholar
  123. Rinnerthaler M, Jarolim S, Heeren G, Palle E, Perju S, Klinger H, Bogengruber E, Madeo F, Braun RJ, Breitenbach-Koller L et al (2006) MMI1 (YKL056c, TMA19), the yeast orthologue of the translationally controlled tumor protein (TCTP) has apoptotic functions and interacts with both microtubules and mitochondria. Biochim Biophys Acta 1757:631–638PubMedGoogle Scholar
  124. Ritch JJ, Davidson SM, Sheehan JJ, Austriaco OPN (2010) The Saccharomyces SUN gene, UTH1, is involved in cell wall biogenesis. Fems Yeast Res 10:168–176PubMedGoogle Scholar
  125. Ruge G (1889) Vorgange am Eifollikel der Wirbelthiere. Morphol Jahrbuch 15:491–554Google Scholar
  126. Scheckhuber CQ, Erjavec N, Tinazli A, Hamann A, Nystrom T, Osiewacz HD (2007) Reducing mitochondrial fission results in increased life span and fitness of two fungal ageing models. Nat Cell Biol 9:99–U129PubMedGoogle Scholar
  127. Schmaus H, Albrecht E (1894) Über Karyrhexis. Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin 138:1–80Google Scholar
  128. Schmitt E, Paquet C, Beauchemin M, Bertrand R (2007) DNA-damage response network at the crossroads of cell-cycle checkpoints, cellular senescence and apoptosis. J Zhejiang Univ Sci B 8:377–397PubMedGoogle Scholar
  129. Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E et al (2007) Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 22:807–818Google Scholar
  130. Severin FF, Hyman AA (2002) Pheromone induces programmed cell death in S. cerevisiae. Curr Biol 12:R233–R235PubMedGoogle Scholar
  131. Singh KK (2004) Mitochondria damage checkpoint in apoptosis and genome stability. FEMS Yeast Res 5:127–132PubMedGoogle Scholar
  132. Skulachev VP (2002) Programmed death in yeast as adaptation? FEBS Lett 528:23–26PubMedGoogle Scholar
  133. Ströbe H (1892) Zur Kenntnis verschiedener cellularer Vorgange und Erscheinungen in Geschwulsten. Beitr Pathol Anat 11:1–38Google Scholar
  134. Sulston JE (1976) Post-embryonic development in the ventral cord of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 275:287–297PubMedGoogle Scholar
  135. Susini L, Besse S, Duflaut D, Lespagnol A, Beekman C, Fiucci G, Atkinson AR, Busso D, Poussin P, Marine JC et al (2008) TCTP protects from apoptotic cell death by antagonizing bax function. Cell Death Differ 15:1211–1220PubMedGoogle Scholar
  136. Syntichaki P, Troulinaki K, Tavernarakis N (2007) eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445:922–926PubMedGoogle Scholar
  137. Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci USA 45:30–45PubMedGoogle Scholar
  138. Thedieck K, Polak P, Kim ML, Molle KD, Cohen A, Jeno P, Arrieumerlou C, Hall MN (2007) PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis. Plos One 2:e1217PubMedGoogle Scholar
  139. Tsujimoto Y, Croce CM (1986) Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci USA 83:5214–5218PubMedGoogle Scholar
  140. Uren AG, O’Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM (2000) Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 6:961–967PubMedGoogle Scholar
  141. Vaux DL, Cory S, Adams JM (1988) Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335:440–442PubMedGoogle Scholar
  142. Vijg J (2000) Somatic mutations and aging: a re-evaluation. Mutat Res 447:117–135PubMedGoogle Scholar
  143. Vogt C (1842) Untersuchungen uber die Entwicklungsgeschichte der Geburtshelerkroete (Alytes obstetricians). Jent und Gassman, SolothurnGoogle Scholar
  144. Wadskog I, Maldener C, Proksch A, Madeo F, Adler L (2004) Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress. Mol Biol Cell 15:1436–1444PubMedGoogle Scholar
  145. Walter D, Matter A, Fahrenkrog B (2010) Bre1p-mediated histone H2B ubiquitylation regulates apoptosis in Saccharomyces cerevisiae. J Cell Sci 123:1931–1939PubMedGoogle Scholar
  146. Walter D, Wissing S, Madeo F, Fahrenkrog B (2006) The inhibitor-of-apoptosis protein Bir1p protects against apoptosis in S. cerevisiae and is a substrate for the yeast homologue of Omi/HtrA2. J Cell Sci 119:1843–1851PubMedGoogle Scholar
  147. Wang YB, Lou Y, Luo ZF, Zhang DF, Wang YZ (2003) Induction of apoptosis and cell cycle arrest by polyvinylpyrrolidone K-30 and protective effect of alpha-tocopherol. Biochem Biophys Res Commun 308:878–884PubMedGoogle Scholar
  148. Weigert K (1880) Ueber die pathologische Gerinnungs-Vorgänge. Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin 79:87–123Google Scholar
  149. Weinberger M, Feng L, Paul A, Smith DL, Jr, Hontz RD, Smith JS, Vujcic M, Singh KK, Huberman JA, Burhans WC (2007) DNA replication stress is a determinant of chronological lifespan in budding yeast. Plos One 2:e748PubMedGoogle Scholar
  150. Weinberger M, Mesquita A, Caroll T, Marks L, Yang H, Zhang Z, Ludovico P, Burhans WC (2010) Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence. Aging (Albany NY) 2:709–726Google Scholar
  151. Weinberger M, Ramachandran L, Feng L, Sharma K, Sun X, Marchetti M, Huberman JA, Burhans WC (2005) Apoptosis in budding yeast caused by defects in initiation of DNA replication. J Cell Sci 118:3543–3553PubMedGoogle Scholar
  152. Weng YF, Xiang L, Matsuura A, Zhang Y, Huang QM, Qi JH (2010) Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene. Bioorgan Med Chem 18:999–1002Google Scholar
  153. Williams GC (2001) Pleiotropy, natural selection, and the evolution of senescence. Sci Aging Knowl Environ 2001:cp13Google Scholar
  154. Williams JR, Little JB, Shipley WU (1974) Association of mammalian cell death with a specific endonucleolytic degradation of DNA. Nature 252:754–755PubMedGoogle Scholar
  155. Winkler J, Seybert A, Konig L, Pruggnaller S, Haselmann U, Sourjik V, Weiss M, Frangakis AS, Mogk A, Bukau B (2010) Quantitative and spatio-temporal features of protein aggregation in Escherichia coli and consequences on protein quality control and cellular ageing. EMBO J 29:910–923PubMedGoogle Scholar
  156. Wissing S, Ludovico P, Herker E, Buttner S, Engelhardt SM, Decker T, Link A, Proksch A, Rodrigues F, Corte-Real M et al (2004) An AIF orthologue regulates apoptosis in yeast. J Cell Biol 166:969–974PubMedGoogle Scholar
  157. Wood W, Turmaine M, Weber R, Camp V, Maki RA, McKercher SR, Martin P (2000) Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development 127:5245–5252PubMedGoogle Scholar
  158. Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556PubMedGoogle Scholar
  159. Yamaki M, Umehara T, Chimura T, Horikoshi M (2001) Cell death with predominant apoptotic features in Saccharomyces cerevisiae mediated by deletion of the histone chaperone ASF1/CIA1. Genes Cells 6:1043–1054PubMedGoogle Scholar
  160. Yang Y, Yang F, Xiong ZY, Yan Y, Wang XM, Nishino M, Mirkovic D, Nguyen J, Wang H, Yang XF (2005) An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity. Oncogene 24:4778–4788PubMedGoogle Scholar
  161. Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A, Oren M (1991) Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352:345–347PubMedGoogle Scholar
  162. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75:641–652PubMedGoogle Scholar
  163. Zassenhaus HP, Denniger G (1994) Analysis of the role of the NUC1 endo/exonuclease in yeast mitochondrial DNA recombination. Curr Genet 25:142–149PubMedGoogle Scholar
  164. Zhang Y, Herman B (2002) Ageing and apoptosis. Mech Ageing Dev 123:245–260PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Peter Laun
    • 1
    Email author
  • Sabrina Büttner
    • 2
  • Mark Rinnerthaler
    • 1
  • William C. Burhans
    • 3
  • Michael Breitenbach
    • 1
  1. 1.Division of Genetics, Department of Cell BiologyUniversity of SalzburgSalzburgAustria
  2. 2.Institute of Molecular BiosciencesUniversity of GrazGrazAustria
  3. 3.Department of Molecular and Cellular BiologyRoswell Park Cancer InstituteBuffaloUSA

Personalised recommendations