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The Role of Mitochondria in the Aging Processes of Yeast

  • Michael BreitenbachEmail author
  • Peter Laun
  • J. Richard Dickinson
  • Andrea Klocker
  • Mark Rinnerthaler
  • Ian W. Dawes
  • May T. Aung-Htut
  • Lore Breitenbach-Koller
  • Antonio Caballero
  • Thomas Nyström
  • Sabrina Büttner
  • Tobias Eisenberg
  • Frank Madeo
  • Markus Ralser
Part of the Subcellular Biochemistry book series (SCBI, volume 57)

Abstract

This chapter reviews the role of mitochondria and of mitochondrial metabolism in the aging processes of yeast and the existing evidence for the “mitochondrial theory of aging ”. Mitochondria are the major source of ATP in the eukaryotic cell but are also a major source of reactive oxygen species (ROS) and play an important role in the process of apoptosis and aging. We are discussing the mitochondrial theory of aging (TOA), its origin, similarity with other TOAs, and its ramifications which developed in recent decades. The emphasis is on mother cell-specific aging and the RLS (replicative lifespan) with only a short treatment of CLS (chronological lifespan). Both of these aging processes may be relevant to understand also the aging of higher organisms, but they are biochemically very different, as shown by the fact the replicative aging occurs on rich media and is a defect in the replicative capacity of mother cells, while chronological aging occurs in postmitotic cells that are under starvation conditions in stationary phase leading to loss of viability, as discussed elsewhere in this book. In so doing we also give an overview of the similarities and dissimilarities of the various aging processes of the most often used model organisms for aging research with respect to the mitochondrial theory of aging .

Keywords

Mitochondria Mutation DNA repair Somatic mutation theory Hypoxia 

References

  1. Aguilaniu H, Gustafsson L, Rigoulet M, Nystrom T (2003) Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299:1751–1753PubMedGoogle Scholar
  2. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA (2003) Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423:181–185PubMedGoogle Scholar
  3. Baker MJ, Frazier AE, Gulbis JM, Ryan MT (2007) Mitochondrial protein-import machinery: correlating structure with function. Trends Cell Biol 17:456–464PubMedGoogle Scholar
  4. Berra E, Ginouves A, Pouyssegur J (2006) The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling. EMBO Rep 7:41–45PubMedGoogle Scholar
  5. Bhatia-Kissova I, Camougrand N (2010) Mitophagy in yeast: actors and physiological roles. FEMS Yeast Res 10:1023–1034PubMedGoogle Scholar
  6. Boveris A, Navarro A (2008) Brain mitochondrial dysfunction in aging. IUBMB Life 60:308–314PubMedGoogle Scholar
  7. 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
  8. Buetler TM, Krauskopf A, Ruegg UT (2004) Role of superoxide as a signaling molecule. News Physiol Sci 19:120–123PubMedGoogle Scholar
  9. Butow RA, Avadhani NG (2004) Mitochondrial signaling: the retrograde response. Mol Cell 14:1–15PubMedGoogle Scholar
  10. 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
  11. Caballero A, Ugidos A, Liu B, Öling D, Kvint K, Hao X, Mignat C, Nachin L, Molin M, Nyström T (2011) Absence of mitochondrial translation control proteins extend life span by activating sirtuin-dependent silencing. Mol Cell 42:390–400Google Scholar
  12. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230PubMedGoogle Scholar
  13. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605PubMedGoogle Scholar
  14. Chen D, Thomas EL, Kapahi P (2009) HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet 5:e1000486PubMedGoogle Scholar
  15. Chen JB, Sun J, Jazwinski SM (1990) Prolongation of the yeast life span by the v-Ha-RAS oncogene. Mol Microbiol 4:2081–2086PubMedGoogle Scholar
  16. Dann SG, Thomas G (2006) The amino acid sensitive TOR pathway from yeast to mammals. FEBS Lett 580:2821–2829PubMedGoogle Scholar
  17. Deffieu M, Bhatia-Kissova I, Salin B, Galinier A, Manon S, Camougrand N (2009) Glutathione participates in the regulation of mitophagy in yeast. J Biol Chem 284:14828–14837PubMedGoogle Scholar
  18. Edgar D, Larsson NG, Trifunovic A (2010) Response: point mutations are causing progeroid phenotypes in the mtDNA mutator mouse. Cell Metab 11:93PubMedGoogle Scholar
  19. Edgar D, Shabalina I, Camara Y, Wredenberg A, Calvaruso MA, Nijtmans L, Nedergaard J, Cannon B, Larsson NG, Trifunovic A (2009) Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab 10:131–138PubMedGoogle Scholar
  20. Eisenberg T, Carmona-Gutierrez D, Buttner S, Tavernarakis N, Madeo F (2010) Necrosis in yeast. Apoptosis 15:257–268PubMedGoogle Scholar
  21. Eisenberg T, Knauer H, Schauer A, Buttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L, Fussi H, Deszcz L, Hartl R, Schraml E, Criollo A, Megalou E, Weiskopf D, Laun P, Heeren G, Breitenbach M, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Frohlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11:1305–1314PubMedGoogle Scholar
  22. Erjavec N, Cvijovic M, Klipp E, Nystrom T (2008) Selective benefits of damage partitioning in unicellular systems and its effects on aging. Proc Natl Acad Sci USA 105:18764–18769PubMedGoogle Scholar
  23. 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
  24. Fabrizio P, Hoon S, Shamalnasab M, Galbani A, Wei M, Giaever G, Nislow C, Longo VD (2010) Genome-wide screen in Saccharomyces cerevisiae identifies vacuolar protein sorting, autophagy, biosynthetic, and tRNA methylation genes involved in life span regulation. PLoS Genet 6:e1001024PubMedGoogle Scholar
  25. Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD (2001) Regulation of longevity and stress resistance by Sch9 in yeast. Science 292:288–290PubMedGoogle Scholar
  26. Fox TD (1996) Genetic strategies for identification of mitochondrial translation factors in Saccharomyces cerevisiae. Meth Enzymol 264:228–237PubMedGoogle Scholar
  27. Gallo CM, Smith DL Jr, Smith JS (2004) Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity. Mol Cell Biol 24:1301–1312PubMedGoogle Scholar
  28. Gerschman R, Gilbert DL, Nye SW, Dwyer P, Fenn WO (1954) Oxygen poisoning and x-irradiation: a mechanism in common. Science 119:623–626PubMedGoogle Scholar
  29. Gourlay CW, Ayscough KR (2006) Actin-induced hyperactivation of the Ras signaling pathway leads to apoptosis in Saccharomyces cerevisiae. Mol Cell Biol 26:6487–6501PubMedGoogle Scholar
  30. Grivell LA, Artal-Sanz M, Hakkaart G, de Jong L, Nijtmans LG, van Oosterum K, Siep M, van der Spek H (1999) Mitochondrial assembly in yeast. FEBS Lett 452:57–60PubMedGoogle Scholar
  31. Halliwell B, Gutteridge JM (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1–14PubMedGoogle Scholar
  32. Halliwell B, Gutteridge JM (1988) Free radicals and antioxidant protection: mechanisms and significance in toxicology and disease. Hum Toxicol 7:7–13PubMedGoogle Scholar
  33. Halliwell B, Gutteridge JM, Aruoma OI (1987) The deoxyribose method: a simple “test-tube” assay for determination of rate constants for reactions of hydroxyl radicals. Anal Biochem 165:215–219PubMedGoogle Scholar
  34. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300PubMedGoogle Scholar
  35. Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147PubMedGoogle Scholar
  36. Heeren G, Rinnerthaler M, Laun P, von Seyerl P, Kossler S, Klinger H, Hager M, Bogengruber E, Jarolim S, Simon-Nobbe B, Schuller C, Carmona-Gutierrez D, Breitenbach-Koller L, Muck C, Jansen-Durr P, Criollo A, Kroemer G, Madeo F, Breitenbach M (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
  37. 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
  38. Hlavata L, Nachin L, Jezek P, Nystrom T (2008) Elevated Ras/protein kinase A activity in Saccharomyces cerevisiae reduces proliferation rate and lifespan by two different reactive oxygen species-dependent routes. Aging Cell 7:148–157PubMedGoogle Scholar
  39. Jazwinski SM (2004) Yeast replicative life span – the mitochondrial connection. FEMS Yeast Res 5:119–125PubMedGoogle Scholar
  40. Jazwinski SM (2005a) The retrograde response links metabolism with stress responses, chromatin-dependent gene activation, and genome stability in yeast aging. Gene 354:22–27PubMedGoogle Scholar
  41. Jazwinski SM (2005b) Rtg2 protein: at the nexus of yeast longevity and aging. FEMS Yeast Res 5:1253–1259PubMedGoogle Scholar
  42. Jazwinski SM (2005c) Yeast longevity and aging – the mitochondrial connection. Mech Ageing Dev 126:243–248PubMedGoogle Scholar
  43. Jiang JC, Jaruga E, Repnevskaya MV, Jazwinski SM (2000) An intervention resembling caloric restriction prolongs life span and retards aging in yeast. FASEB J 14:2135–2137PubMedGoogle Scholar
  44. Jungwirth H, Ring J, Mayer T, Schauer A, Buttner S, Eisenberg T, Carmona-Gutierrez D, Kuchler K, Madeo F (2008) Loss of peroxisome function triggers necrosis. FEBS Lett 582:2882–2886PubMedGoogle Scholar
  45. Kaeberlein M, Kapahi P (2009) The hypoxic response and aging. Cell Cycle 8:2324PubMedGoogle Scholar
  46. Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310:1193–1196PubMedGoogle Scholar
  47. Kanki T, Klionsky DJ (2008) Mitophagy in yeast occurs through a selective mechanism. J Biol Chem 283:32386–32393PubMedGoogle Scholar
  48. Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ (2009) Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell 17:98–109PubMedGoogle Scholar
  49. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11:453–465PubMedGoogle Scholar
  50. Khrapko K, Kraytsberg Y, de Grey AD, Vijg J, Schon EA (2006) Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging? Aging Cell 5:279–282PubMedGoogle Scholar
  51. Khrapko K, Vijg J (2007) Mitochondrial DNA mutations and aging: a case closed? Nat Genet 39:445–446PubMedGoogle Scholar
  52. Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462:245–253PubMedGoogle Scholar
  53. Kirchman PA, Kim S, Lai CY, Jazwinski SM (1999) Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae. Genetics 152:179–190PubMedGoogle Scholar
  54. Kissova I, Salin B, Schaeffer J, Bhatia S, Manon S, Camougrand N (2007) Selective and non-selective autophagic degradation of mitochondria in yeast. Autophagy 3:329–336PubMedGoogle Scholar
  55. 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
  56. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484PubMedGoogle Scholar
  57. Lai CY, Jaruga E, Borghouts C, Jazwinski SM (2002) A mutation in the ATP2 gene abrogates the age asymmetry between mother and daughter cells of the yeast Saccharomyces cerevisiae. Genetics 162:73–87PubMedGoogle Scholar
  58. Lam YT, Stocker R, Dawes IW (2010) The lipophilic antioxidants alpha-tocopherol and coenzyme Q10 reduce the replicative lifespan of Saccharomyces cerevisiae. Free Radic Biol Med 49:237–244PubMedGoogle Scholar
  59. Lane N, Martin W (2010) The energetics of genome complexity. Nature 467:929–934PubMedGoogle Scholar
  60. Lang BF, Burger G, O’Kelly CJ, Cedergren R, Golding GB, Lemieux C, Sankoff D, Turmel M, Gray MW (1997) An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387:493–497PubMedGoogle Scholar
  61. 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
  62. 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
  63. Leadsham JE, Miller K, Ayscough KR, Colombo S, Martegani E, Sudbery P, Gourlay CW (2009) Whi2p links nutritional sensing to actin-dependent Ras-cAMP-PKA regulation and apoptosis in yeast. J Cell Sci 122:706–715PubMedGoogle Scholar
  64. Lee J, Moir RD, Willis IM (2009) Regulation of RNA polymerase III transcription involves SCH9-dependent and SCH9-independent branches of the target of rapamycin (TOR) pathway. J Biol Chem 284:12604–12608PubMedGoogle Scholar
  65. Lee SJ, Hwang AB, Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20:2131–2136PubMedGoogle Scholar
  66. 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
  67. Liao X, Butow RA (1993) RTG1 and RTG2: two yeast genes required for a novel path of communication from mitochondria to the nucleus. Cell 72:61–71PubMedGoogle Scholar
  68. 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
  69. Liu Z, Butow RA (2006) Mitochondrial retrograde signaling. Annu Rev Genet 40:159–185PubMedGoogle Scholar
  70. Longo VD (1999) Mutations in signal transduction proteins increase stress resistance and longevity in yeast, nematodes, fruit flies, and mammalian neuronal cells. Neurobiol Aging 20:479–486PubMedGoogle Scholar
  71. 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
  72. Luttik MA, Overkamp KM, Kotter P, de Vries S, van Dijken JP, Pronk JT (1998) The Saccharomyces cerevisiae NDE1 and NDE2 genes encode separate mitochondrial NADH dehydrogenases catalyzing the oxidation of cytosolic NADH. J Biol Chem 273:24529–24534PubMedGoogle Scholar
  73. 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
  74. 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
  75. Madeo F, Herker E, Maldener C, Wissing S, Lachelt S, Herlan M, Fehr M, Lauber K, Sigrist SJ, Wesselborg S, Frohlich KU (2002) A caspase-related protease regulates apoptosis in yeast. Mol Cell 9:911–917PubMedGoogle Scholar
  76. Madia F, Wei M, Yuan V, Hu J, Gattazzo C, Pham P, Goodman MF, Longo VD (2009) Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Polzeta-dependent mechanism. J Cell Biol 186:509–523PubMedGoogle Scholar
  77. Marres CA, de Vries S, Grivell LA (1991) Isolation and inactivation of the nuclear gene encoding the rotenone-insensitive internal NADH: ubiquinone oxidoreductase of mitochondria from Saccharomyces cerevisiae. Eur J Biochem 195:857–862PubMedGoogle Scholar
  78. McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055PubMedGoogle Scholar
  79. McMurray MA, Gottschling DE (2003) An age-induced switch to a hyper-recombinational state. Science 301:1908–1911PubMedGoogle Scholar
  80. Medvedik O, Lamming DW, Kim KD, Sinclair DA (2007) MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol 5:e261PubMedGoogle Scholar
  81. Mehta R, Steinkraus KA, Sutphin GL, Ramos FJ, Shamieh LS, Huh A, Davis C, Chandler-Brown D, Kaeberlein M (2009) Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science 324:1196–1198PubMedGoogle Scholar
  82. Merz S, Westermann B (2009) Genome-wide deletion mutant analysis reveals genes required for respiratory growth, mitochondrial genome maintenance and mitochondrial protein synthesis in Saccharomyces cerevisiae. Genome Biol 10:R95PubMedGoogle Scholar
  83. Mesquita A, Weinberger M, Silva A, Sampaio-Marques B, Almeida B, Leao C, Costa V, Rodrigues F, Burhans WC, Ludovico P (2010) Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity. Proc Natl Acad Sci USA 107:15123–15128PubMedGoogle Scholar
  84. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–148PubMedGoogle Scholar
  85. Muller FL, Song W, Jang YC, Liu Y, Sabia M, Richardson A, Van Remmen H (2007) Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production. Am J Physiol Regul Integr Comp Physiol 293:R1159–1168PubMedGoogle Scholar
  86. Muller I (1971) Experiments on ageing in single cells of Saccharomyces cerevisiae. Arch Mikrobiol 77:20–25PubMedGoogle Scholar
  87. Muller RU, Fabretti F, Zank S, Burst V, Benzing T, Schermer B (2009) The von Hippel Lindau tumor suppressor limits longevity. J Am Soc Nephrol 20:2513–2517PubMedGoogle Scholar
  88. Nair U, Klionsky DJ (2005) Molecular mechanisms and regulation of specific and nonspecific autophagy pathways in yeast. J Biol Chem 280:41785–41788PubMedGoogle Scholar
  89. Naithani S, Saracco SA, Butler CA, Fox TD (2003) Interactions among COX1, COX2, and COX3 mRNA-specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae. Mol Biol Cell 14:324–333PubMedGoogle Scholar
  90. Nestelbacher R, Laun P, Vondrakova D, Pichova A, Schuller C, Breitenbach M (2000) The influence of oxygen toxicity on yeast mother cell-specific aging. Exp Gerontol 35:63–70PubMedGoogle Scholar
  91. Nowikovsky K, Reipert S, Devenish RJ, Schweyen RJ (2007) Mdm38 protein depletion causes loss of mitochondrial K+/H+ exchange activity, osmotic swelling and mitophagy. Cell Death Differ 14:1647–1656PubMedGoogle Scholar
  92. Nystrom T (2007) A bacterial kind of aging. PLoS Genet 3:e224PubMedGoogle Scholar
  93. Ohlmeier S, Kastaniotis AJ, Hiltunen JK, Bergmann U (2004) The yeast mitochondrial proteome, a study of fermentative and respiratory growth. J Biol Chem 279:3956–3979PubMedGoogle Scholar
  94. 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
  95. Park SK, Link CD, Johnson TE (2009) Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J 24:383–392PubMedGoogle Scholar
  96. Parrella E, Longo VD (2008) The chronological life span of Saccharomyces cerevisiae to study mitochondrial dysfunction and disease. Methods 46:256–262PubMedGoogle Scholar
  97. Perez-Martinez X, Broadley SA, Fox TD (2003) Mss51p promotes mitochondrial Cox1p synthesis and interacts with newly synthesized Cox1p. EMBO J 22:5951–5961PubMedGoogle Scholar
  98. Perocchi F, Jensen LJ, Gagneur J, Ahting U, von Mering C, Bork P, Prokisch H, Steinmetz LM (2006) Assessing systems properties of yeast mitochondria through an interaction map of the organelle. PLoS Genet 2:e170PubMedGoogle Scholar
  99. 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
  100. Powers RW 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 20:174–184PubMedGoogle Scholar
  101. Racker E (1977) Mechanisms of energy transformations. Annu Rev Biochem 46:1006–1014PubMedGoogle Scholar
  102. Ralser M, Heeren G, Breitenbach M, Lehrach H, Krobitsch S (2006) Triose phosphate isomerase deficiency is caused by altered dimerization – not catalytic inactivity – of the mutant enzymes. PLoS One 1:e30PubMedGoogle Scholar
  103. Ratcliffe PJ (2006) Understanding hypoxia signalling in cells – a new therapeutic opportunity? Clin Med 6:573–578Google Scholar
  104. Rinnerthaler M, Jarolim S, Heeren G, Palle E, Perju S, Klinger H, Bogengruber E, Madeo F, Braun RJ, Breitenbach-Koller L, Breitenbach M, Laun P (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
  105. Ruckenstuhl C, Buttner S, Carmona-Gutierrez D, Eisenberg T, Kroemer G, Sigrist SJ, Frohlich KU, Madeo F (2009) The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer. PLoS One 4:e4592PubMedGoogle Scholar
  106. Schafer FQ, Buettner GR (2000) Acidic pH amplifies iron-mediated lipid peroxidation in cells. Free Radic Biol Med 28:1175–1181PubMedGoogle Scholar
  107. Schmidt O, Pfanner N, Meisinger C (2010) Mitochondrial protein import: from proteomics to functional mechanisms. Nat Rev Mol Cell Biol 11:655–667PubMedGoogle Scholar
  108. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911PubMedGoogle Scholar
  109. Steinkraus KA, Kaeberlein M, Kennedy BK (2008) Replicative aging in yeast: the means to the end. Annu Rev Cell Dev Biol 24:29–54PubMedGoogle Scholar
  110. Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci USA 45:30–45PubMedGoogle Scholar
  111. Takemoto D, Tanaka A, Scott B (2007) NADPH oxidases in fungi: diverse roles of reactive oxygen species in fungal cellular differentiation. Fungal Genet Biol 44:1065–1076PubMedGoogle Scholar
  112. Thorpe GW, Fong CS, Alic N, Higgins VJ, Dawes IW (2004) Cells have distinct mechanisms to maintain protection against different reactive oxygen species: oxidative-stress-response genes. Proc Natl Acad Sci USA 101:6564–6569PubMedGoogle Scholar
  113. Timmermann B, Jarolim S, Russmayer H, Kerick M, Michel S, Kruger A, Bluemlein K, Laun P, Grillari J, Lehrach H, Breitenbach M, Ralser M (2010) A new dominant peroxiredoxin allele identified by whole-genome re-sequencing of random mutagenized yeast causes oxidant-resistance and premature aging. Aging (Albany NY) 2:475–486Google Scholar
  114. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:417–423PubMedGoogle Scholar
  115. Ugidos A, Nystrom T, Caballero A (2010) Perspectives on the mitochondrial etiology of replicative aging in yeast. Exp Gerontol 45:512–515PubMedGoogle Scholar
  116. Veatch JR, McMurray MA, Nelson ZW, Gottschling DE (2009) Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect. Cell 137:1247–1258PubMedGoogle Scholar
  117. Vermulst M, Bielas JH, Kujoth GC, Ladiges WC, Rabinovitch PS, Prolla TA, Loeb LA (2007) Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet 39:540–543PubMedGoogle Scholar
  118. Vermulst M, Wanagat J, Kujoth GC, Bielas JH, Rabinovitch PS, Prolla TA, Loeb LA (2008) DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet 40:392–394PubMedGoogle Scholar
  119. Vigne P, Frelin C (2007) Plasticity of the responses to chronic hypoxia and dietary restriction in an aged organism: evidence from the Drosophila model. Exp Gerontol 42:1162–1166PubMedGoogle Scholar
  120. Williams SL, Huang J, Edwards YJ, Ulloa RH, Dillon LM, Prolla TA, Vance JM, Moraes CT, Zuchner S (2010) The mtDNA mutation spectrum of the progeroid Polg mutator mouse includes abundant control region multimers. Cell Metab 12:675–682PubMedGoogle Scholar
  121. Xie MW, Jin F, Hwang H, Hwang S, Anand V, Duncan MC, Huang J (2005) Insights into TOR function and rapamycin response: chemical genomic profiling by using a high-density cell array method. Proc Natl Acad Sci USA 102:7215–7220PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Michael Breitenbach
    • 1
    Email author
  • Peter Laun
    • 1
  • J. Richard Dickinson
    • 2
  • Andrea Klocker
    • 1
  • Mark Rinnerthaler
    • 1
  • Ian W. Dawes
    • 3
  • May T. Aung-Htut
    • 3
  • Lore Breitenbach-Koller
    • 1
  • Antonio Caballero
    • 4
  • Thomas Nyström
    • 5
  • Sabrina Büttner
    • 6
  • Tobias Eisenberg
    • 6
  • Frank Madeo
    • 6
  • Markus Ralser
    • 7
  1. 1.Division of Genetics, Department of Cell BiologyUniversity of SalzburgSalzburgAustria
  2. 2.Department of BiochemistryCambridge Systems Biology Centre, University of CambridgeCambridgeUK
  3. 3.School of Biotechnology and Biomolecular SciencesUniversity of New South WalesSydneyAustralia
  4. 4.MRC Centre for Developmental Neurobiology, Guy’s Campus, King’s College LondonLondonUK
  5. 5.Department of Cell and Molecular Biology (CMB)University of GothenburgGöteborgSweden
  6. 6.Institute of Molecular Biosciences, University of GrazGrazAustria
  7. 7.Max Planck Institute for Molecular GeneticsBerlinGermany

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