Table of Contents Author Guidelines Submit a Manuscript
Journal of Aging Research
Volume 2011 (2011), Article ID 234875, 13 pages
http://dx.doi.org/10.4061/2011/234875
Review Article

Mitochondrial Acetylation and Diseases of Aging

1Department of Medical & Molecular Genetics, Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2Department of Pediatrics, Riley Heart Research Center, Wells Center for Pediatric Research, Indiana University School of Medicine, IN 46202, USA

Received 22 October 2010; Accepted 8 January 2011

Academic Editor: Alberto Sanz

Copyright © 2011 Gregory R. Wagner and R. Mark Payne. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. D. Strahl and C. D. Allis, “The language of covalent histone modifications,” Nature, vol. 403, no. 6765, pp. 41–45, 2000. View at Publisher · View at Google Scholar · View at Scopus
  2. S. C. Kim, R. Sprung, Y. Chen et al., “Substrate and functional diversity of lysine acetylation revealed by a proteomics survey,” Molecular Cell, vol. 23, no. 4, pp. 607–618, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. Q. Wang, Y. Zhang, C. Yang et al., “Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux,” Science, vol. 327, no. 5968, pp. 1004–1007, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. M. D. Hirschey, T. Shimazu, E. Goetzman et al., “SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation,” Nature, vol. 464, no. 1, pp. 121–125, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Schlicker, M. Gertz, P. Papatheodorou, B. Kachholz, C. F. W. Becker, and C. Steegborn, “Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5,” Journal of Molecular Biology, vol. 382, no. 3, pp. 790–801, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. T. Nakagawa, D. J. Lomb, M. C. Haigis, and L. Guarente, “SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle,” Cell, vol. 137, no. 3, pp. 560–570, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. B. H. Ahn, H. S. Kim, S. Song et al., “A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 38, pp. 14447–14452, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. L. Guarente, “Calorie restriction and SIR2 genes—towards a mechanism,” Mechanisms of Ageing and Development, vol. 126, no. 9, pp. 923–928, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. M. C. Haigis and L. P. Guarente, “Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction,” Genes and Development, vol. 20, no. 21, pp. 2913–2921, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. H. A. Krebs, “The citric acid cycle and the Szent-Györgyi cycle in pigeon breast muscle,” Biochemical Journal, vol. 34, no. 5, pp. 775–779, 1940. View at Google Scholar
  11. P. Mitchell, “Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism,” Nature, vol. 191, no. 4784, pp. 144–148, 1961. View at Publisher · View at Google Scholar · View at Scopus
  12. D. E. Bauer, G. Hatzivassiliou, F. Zhao, C. Andreadis, and C. B. Thompson, “ATP citrate lyase is an important component of cell growth and transformation,” Oncogene, vol. 24, no. 41, pp. 6314–6322, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. K. Bloch, “The biological synthesis of cholesterol,” Science, vol. 150, no. 3692, pp. 19–28, 1965. View at Google Scholar · View at Scopus
  14. P. A. Edwards and J. Ericsson, “Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway,” Annual Review of Biochemistry, vol. 68, pp. 157–185, 1999. View at Publisher · View at Google Scholar · View at Scopus
  15. R. Nosadini, A. Avogaro, A. Doria, P. Fioretto, R. Trevisan, and A. Morocutti, “Ketone body metabolism: a physiological and clinical overview,” Diabetes/Metabolism Reviews, vol. 5, no. 3, pp. 299–319, 1989. View at Google Scholar · View at Scopus
  16. A. Luong, V. C. Hannah, M. S. Brown, and J. L. Goldstein, “Molecular characterization of human acetyl-CoA synthetase, an enzyme regulated by sterol regulatory element-binding proteins,” Journal of Biological Chemistry, vol. 275, no. 34, pp. 26458–26466, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Fujino, J. Kondo, M. Ishikawa, K. Morikawa, and T. T. Yamamoto, “Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate,” Journal of Biological Chemistry, vol. 276, no. 14, pp. 11420–11426, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. I. Sakakibara, T. Fujino, M. Ishii et al., “Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2,” Cell Metabolism, vol. 9, no. 2, pp. 191–202, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. K. E. Wellen, G. Hatzivassiliou, U. M. Sachdeva, T. V. Bui, J. R. Cross, and C. B. Thompson, “ATP-citrate lyase links cellular metabolism to histone acetylation,” Science, vol. 324, no. 5930, pp. 1076–1080, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. E. L. Gershey, G. Vidali, and V. G. Allfrey, “Chemical studies of histone acetylation. The occurrence of epsilon-N-acetyllysine in the f2a1 histone,” Journal of Biological Chemistry, vol. 243, no. 19, pp. 5018–5022, 1968. View at Google Scholar · View at Scopus
  21. A. Inoue and D. Fujimoto, “Enzymatic deacetylation of histone,” Biochemical and Biophysical Research Communications, vol. 36, no. 1, pp. 146–150, 1969. View at Google Scholar · View at Scopus
  22. D. Fujimoto and K. Segawa, “Enzymatic deacetylation of f2a2 histone,” FEBS Letters, vol. 32, no. 1, pp. 59–61, 1973. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Kervabon, J. Mery, and J. Parello, “Enzymatic deacetylation of a synthetic peptide fragment of histone H4,” FEBS Letters, vol. 106, no. 1, pp. 93–96, 1979. View at Google Scholar · View at Scopus
  24. J. Taunton, C. A. Hassig, and S. L. Schreiber, “A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p,” Science, vol. 272, no. 5260, pp. 408–411, 1996. View at Google Scholar · View at Scopus
  25. T. Jenuwein and C. D. Allis, “Translating the histone code,” Science, vol. 293, no. 5532, pp. 1074–1080, 2001. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Copeland, D. Buglio, and A. Younes, “Histone deacetylase inhibitors in lymphoma,” Current Opinion in Oncology, vol. 22, no. 5, pp. 431–436, 2010. View at Publisher · View at Google Scholar
  27. I. V. Gregoretti, Y. M. Lee, and H. V. Goodson, “Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis,” Journal of Molecular Biology, vol. 338, no. 1, pp. 17–31, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. C. D. Allis, S. L. Berger, J. Cote et al., “New nomenclature for chromatin-modifying enzymes,” Cell, vol. 131, no. 4, pp. 633–636, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. A. J. M. de Ruijter, A. H. van Gennip, H. N. Caron, S. Kemp, and A. B. P. van Kuilenburg, “Histone deacetylases (HDACs): characterization of the classical HDAC family,” Biochemical Journal, vol. 370, no. 3, pp. 737–749, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. A. J. Bannister and E. A. Miska, “Regulation of gene expression by transcription factor acetylation,” Cellular and Molecular Life Sciences, vol. 57, no. 8-9, pp. 1184–1192, 2000. View at Google Scholar · View at Scopus
  31. W. Gu and R. G. Roeder, “Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain,” Cell, vol. 90, no. 4, pp. 595–606, 1997. View at Publisher · View at Google Scholar · View at Scopus
  32. M. A. Glozak, N. Sengupta, X. Zhang, and E. Seto, “Acetylation and deacetylation of non-histone proteins,” Gene, vol. 363, no. 1-2, pp. 15–23, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. P. Bali, M. Pranpat, J. Bradner et al., “Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors,” Journal of Biological Chemistry, vol. 280, no. 29, pp. 26729–26734, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Sekimoto, T. Matsuyama, T. Fukui, and K. Tanizawa, “Evidence for lysine 80 as general base catalyst of leucine dehydrogenase,” Journal of Biological Chemistry, vol. 268, no. 36, pp. 27039–27045, 1993. View at Google Scholar · View at Scopus
  35. W. Yu, Y. Lin, J. Yao et al., “Lysine 88 acetylation negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals,” Journal of Biological Chemistry, vol. 284, no. 20, pp. 13669–13675, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. Z. L. Yuan, Y. J. Guan, D. Chatterjee, and Y. E. Chin, “Stat3 dimerization regulated by reversible acetylation of a single lysine residue,” Science, vol. 307, no. 5707, pp. 269–273, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Sadoul, C. Boyault, M. Pabion, and S. Khochbin, “Regulation of protein turnover by acetyltransferases and deacetylases,” Biochimie, vol. 90, no. 2, pp. 306–312, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. X. J. Yang and E. Seto, “Lysine acetylation: codified crosstalk with other posttranslational modifications,” Molecular Cell, vol. 31, no. 4, pp. 449–461, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. P. Onyango, I. Celic, J. M. McCaffery, J. D. Boeke, and A. P. Feinberg, “SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 21, pp. 13653–13658, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. E. Michishita, J. Y. Park, J. M. Burneskis, J. C. Barrett, and I. Horikawa, “Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins,” Molecular Biology of the Cell, vol. 16, no. 10, pp. 4623–4635, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. K. Aquilano, P. Vigilanza, S. Baldelli, B. Pagliei, G. Rotilio, and M. R. Ciriolo, “Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis,” Journal of Biological Chemistry, vol. 285, no. 28, pp. 21590–21599, 2010. View at Publisher · View at Google Scholar
  42. R. Amat, A. Planavila, S. L. Chen, R. Iglesias, M. Giralt, and F. Villarroya, “SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-γ co-activator-1α(PGC-1α) gene in skeletal muscle through the PGC-1α autoregulatory loop and interaction with MyoD,” Journal of Biological Chemistry, vol. 284, no. 33, pp. 21872–21880, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. N. R. Sundaresan, S. A. Samant, V. B. Pillai, S. B. Rajamohan, and M. P. Gupta, “SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70,” Molecular and Cellular Biology, vol. 28, no. 20, pp. 6384–6401, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Kaidi, B. T. Weinert, C. Choudhary, and S. P. Jackson, “Human SIRT6 promotes DNA end resection through CtIP deacetylation,” Science, vol. 329, no. 5997, pp. 1348–1353, 2010. View at Publisher · View at Google Scholar
  45. E. M. Dioum, R. Chen, M. S. Alexander et al., “Regulation of hypoxia-inducible factor 2α signaling by the stress-responsive deacetylase sirtuin 1,” Science, vol. 324, no. 5932, pp. 1289–1293, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. H.-S. Kim, C. Xiao, R.-H. Wang et al., “Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis,” Cell Metabolism, vol. 12, no. 3, pp. 224–236, 2010. View at Publisher · View at Google Scholar
  47. A. A. Sauve, C. Wolberger, V. L. Schramm, and J. D. Boeke, “The biochemistry of sirtuins,” Annual Review of Biochemistry, vol. 75, pp. 435–465, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Yang and A. A. Sauve, “NAD metabolism and sirtuins: metabolic regulation of protein deacetylation in stress and toxicity,” AAPS Journal, vol. 8, no. 4, pp. E632–E643, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. J. C. Jiang, E. Jaruga, M. V. Repnevskaya, and S. M. Jazwinski, “An intervention resembling caloric restriction prolongs life span and retards aging in yeast,” FASEB Journal, vol. 14, no. 14, pp. 2135–2137, 2000. View at Google Scholar · View at Scopus
  50. W. Mair, P. Goymer, S. D. Pletcher, and L. Partridge, “Demography of dietary restriction and death in Drosophila,” Science, vol. 301, no. 5640, pp. 1731–1733, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Mattison, G. Roth, M. Lane, and D. Ingram, “Dietary restriction in aging nonhuman primates,” Interdisciplinary Topics in Gerontology, vol. 35, pp. 137–158, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. R. Weindruch and R. L. Walford, “Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence,” Science, vol. 215, no. 4538, pp. 1415–1418, 1982. View at Google Scholar · View at Scopus
  53. J. C. Milne and J. M. Denu, “The Sirtuin family: therapeutic targets to treat diseases of aging,” Current Opinion in Chemical Biology, vol. 12, no. 1, pp. 11–17, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Daub, J. V. Olsen, M. Bairlein et al., “Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle,” Molecular Cell, vol. 31, no. 3, pp. 438–448, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. D. Cantu, J. Schaack, and M. Patel, “Oxidative inactivation of mitochondrial aconitase results in iron and H2O2 neurotoxicity in rat primary mesencephalic cultures,” PLoS One, vol. 4, no. 9, Article ID e7095, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. T.-I. Peng and M.-J. Jou, “Oxidative stress caused by mitochondrial calcium overload,” Annals of the New York Academy of Sciences, vol. 1201, pp. 183–188, 2010. View at Publisher · View at Google Scholar
  57. D. Blache, S. Devaux, O. Joubert et al., “Long-term moderate magnesium-deficient diet shows relationships between blood pressure, inflammation and oxidant stress defense in aging rats,” Free Radical Biology and Medicine, vol. 41, no. 2, pp. 277–284, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. T. Shi, F. Wang, E. Stieren, and Q. Tong, “SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes,” Journal of Biological Chemistry, vol. 280, no. 14, pp. 13560–13567, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. B. Schwer, J. Bunkenborg, R. O. Verdin, J. S. Andersen, and E. Verdin, “Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 27, pp. 10224–10229, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. W. C. Hallows, S. Lee, and J. M. Denu, “Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 27, pp. 10230–10235, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. V. J. Starai, I. Celic, R. N. Cole, J. D. Boeke, and J. C. Escalante-Semerena, “Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine,” Science, vol. 298, no. 5602, pp. 2390–2392, 2002. View at Publisher · View at Google Scholar · View at Scopus
  62. B. Schwer, M. Eckersdorff, Y. Li et al., “Calorie restriction alters mitochondrial protein acetylation,” Aging Cell, vol. 8, no. 5, pp. 604–606, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Zhao, W. Xu, W. Jiang et al., “Regulation of cellular metabolism by protein lysine acetylation,” Science, vol. 327, no. 5968, pp. 1000–1004, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. D. B. Lombard, F. W. Alt, H. L. Cheng et al., “Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation,” Molecular and Cellular Biology, vol. 27, no. 24, pp. 8807–8814, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. N. R. Sundaresan, M. Gupta, G. Kim, S. B. Rajamohan, A. Isbatan, and M. P. Gupta, “Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice,” Journal of Clinical Investigation, vol. 119, no. 9, pp. 2758–2771, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. N. Shulga, R. Wilson-Smith, and J. G. Pastorino, “Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria,” Journal of Cell Science, vol. 123, no. 6, pp. 894–902, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. P. Rinaldo and D. Matern, “Disorders of fatty acid transport and mitochondrial oxidation: challenges and dilemmas of metabolic evaluation,” Genetics in Medicine, vol. 2, no. 6, pp. 338–344, 2000. View at Google Scholar · View at Scopus
  68. S. Someya, W. Yu, W. C. Hallows et al., “Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction,” Cell, vol. 143, no. 5, pp. 802–812. View at Publisher · View at Google Scholar
  69. Y. Yang, H. Cimen, M. J. Han et al., “NAD+ -dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10,” Journal of Biological Chemistry, vol. 285, no. 10, pp. 7417–7429, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Cimen, M. J. Han, Y. Yang, Q. Tong, H. Koc, and E. C. Koc, “Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria,” Biochemistry, vol. 49, no. 2, pp. 304–311, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. M. C. Haigis, R. Mostoslavsky, K. M. Haigis et al., “SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells,” Cell, vol. 126, no. 5, pp. 941–954, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. N. Ahuja, B. Schwer, S. Carobbio et al., “Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase,” Journal of Biological Chemistry, vol. 282, no. 46, pp. 33583–33592, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. N. Nasrin, X. Wu, E. Fortier et al., “SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells,” Journal of Biological Chemistry, vol. 285, no. 42, pp. 31995–32002, 2010. View at Publisher · View at Google Scholar
  74. T. Nakagawa and L. Guarente, “Urea cycle regulation by mitochondrial sirtuin, SIRT5,” Aging, vol. 1, no. 6, pp. 578–581, 2009. View at Google Scholar · View at Scopus
  75. S. J. Allison and J. Milner, “SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways,” Cell Cycle, vol. 6, no. 21, pp. 2669–2677, 2007. View at Google Scholar · View at Scopus
  76. H. S. Kim, K. Patel, K. Muldoon-Jacobs et al., “SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress,” Cancer Cell, vol. 17, no. 1, pp. 41–52, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. K. M. Jacobs, J. D. Pennington, K. S. Bisht et al., “SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression,” International Journal of Biological Sciences, vol. 4, no. 5, pp. 291–299, 2008. View at Google Scholar · View at Scopus
  78. X. Qiu, K. Brown, M. D. Hirschey, E. Verdin, and D. Chen, “Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation,” Cell Metabolism, vol. 12, no. 6, pp. 662–667, 2010. View at Publisher · View at Google Scholar
  79. R. Tao, M. C. Coleman, J. D. Pennington et al., “Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress,” Molecular Cell, vol. 40, no. 6, pp. 893–904, 2010. View at Publisher · View at Google Scholar
  80. H. Yang, T. Yang, J. A. Baur et al., “Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival,” Cell, vol. 130, no. 6, pp. 1095–1107, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Li, M. Banck, S. Mujtaba, M.-M. Zhou, M. M. Sugrue, and M. J. Walsh, “p53-Induced growth arrest is regulated by the Mitochondrial SirT3 deacetylase,” PLoS One, vol. 5, no. 5, Article ID e10486, 2010. View at Publisher · View at Google Scholar
  82. Y. Kawamura, Y. Uchijima, N. Horike et al., “Sirt3 protects in vitro—fertilized mouse preimplantation embryos against oxidative stress—induced p53-mediated developmental arrest,” Journal of Clinical Investigation, vol. 120, no. 8, pp. 2817–2828, 2010. View at Publisher · View at Google Scholar
  83. C. Choudhary, C. Kumar, F. Gnad et al., “Lysine acetylation targets protein complexes and co-regulates major cellular functions,” Science, vol. 325, no. 5942, pp. 834–840, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. W. K. Paik, D. Pearson, H. W. Lee, and S. Kim, “Nonenzymatic acetylation of histones with acetyl-CoA,” Biochimica et Biophysica Acta, vol. 213, no. 2, pp. 513–522, 1970. View at Google Scholar · View at Scopus
  85. D. L. Hoyert, M. P. Heron, S. L. Murphy, and H. C. Kung, “Deaths: final data for 2003,” National Vital Statistics Reports, vol. 54, no. 13, pp. 1–120, 2006. View at Google Scholar · View at Scopus
  86. S. Di Donato, “Multisystem manifestations of mitochondrial disorders,” Journal of Neurology, vol. 256, no. 5, pp. 693–710, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. J. S. Ingwall, “Energy metabolism in heart failure and remodelling,” Cardiovascular Research, vol. 81, no. 3, pp. 412–419, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Neubauer, “The failing heart—an engine out of fuel,” The New England Journal of Medicine, vol. 356, no. 11, pp. 1140–1151, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. V. B. Pillai, N. R. Sundaresan, G. Kim et al., “Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway,” Journal of Biological Chemistry, vol. 285, no. 5, pp. 3133–3144, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. C. P. Hsu, S. Oka, D. Shao, N. Hariharan, and J. Sadoshima, “Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes,” Circulation Research, vol. 105, no. 5, pp. 481–491, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Ruzicka, E. Coletta, R. White, R. Davies, H. Haddad, and F. H.H. Leenen, “Effects of ACE inhibitors on cardiac angiotensin II and aldosterone in humans: relevance of lipophilicity and affinity for ACE,” American Journal of Hypertension, vol. 23, no. 11, pp. 1179–1182, 2010. View at Publisher · View at Google Scholar
  92. A. Benigni, D. Corna, C. Zoja et al., “Disruption of the Ang II type 1 receptor promotes longevity in mice,” Journal of Clinical Investigation, vol. 119, no. 3, pp. 524–530, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. R. Ventura-Clapier, A. Garnier, V. Veksler, and F. Joubert, “Bioenergetics of the failing heart,” Biochimica et Biophysica Acta. In press. View at Publisher · View at Google Scholar
  94. R. Ventura-Clapier, A. Garnier, and V. Veksler, “Energy metabolism in heart failure,” Journal of Physiology, vol. 555, no. 1, pp. 1–13, 2004. View at Publisher · View at Google Scholar · View at Scopus
  95. G. D. Lopaschuk, J. R. Ussher, C. D. L. Folmes, J. S. Jaswal, and W. C. Stanley, “Myocardial fatty acid metabolism in health and disease,” Physiological Reviews, vol. 90, no. 1, pp. 207–258, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. G. D. Lopaschuk, D. D. Belke, J. Gamble, T. Itoi, and B. O. Schonekess, “Regulation of fatty acid oxidation in the mammalian heart in health and disease,” Biochimica et Biophysica Acta, vol. 1213, no. 3, pp. 263–276, 1994. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Neubauer, “The failing heart—an engine out of fuel,” The New England Journal of Medicine, vol. 356, no. 11, pp. 1140–1151, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. M. G. Rosca, E. J. Vazquez, J. Kerner et al., “Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation,” Cardiovascular Research, vol. 80, no. 1, pp. 30–39, 2008. View at Publisher · View at Google Scholar · View at Scopus
  99. M. F. Allard, B. O. Schonekess, S. L. Henning, D. R. English, and G. D. Lopaschuk, “Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts,” American Journal of Physiology, vol. 267, no. 2, pp. H742–H750, 1994. View at Google Scholar · View at Scopus
  100. V. G. Sharov, A. Goussev, M. Lesch, S. Goldstein, and H. N. Sabbah, “Abnormal mitochondrial function in myocardium of dogs with chronic heart failure,” Journal of Molecular and Cellular Cardiology, vol. 30, no. 9, pp. 1757–1762, 1998. View at Publisher · View at Google Scholar · View at Scopus
  101. H. Taegtmeyer, “Cardiac metabolism as a target for the treatment of heart failure,” Circulation, vol. 110, no. 8, pp. 894–896, 2004. View at Publisher · View at Google Scholar · View at Scopus
  102. K. P. O. Warburg and E. Negelein, “Ueber den Stoffwechsel der Tumoren,” Biochemische Zeitschrift, vol. 152, pp. 319–344, 1924. View at Google Scholar
  103. O. Warburg, “On the origin of cancer cells,” Science, vol. 123, no. 3191, pp. 309–314, 1956. View at Google Scholar · View at Scopus
  104. S. Mazurek, C. B. Boschek, F. Hugo, and E. Eigenbrodt, “Pyruvate kinase type M2 and its role in tumor growth and spreading,” Seminars in Cancer Biology, vol. 15, no. 4, pp. 300–308, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. H. R. Christofk, M. G. Vander Heiden, M. H. Harris et al., “The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth,” Nature, vol. 452, no. 7184, pp. 230–233, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. M. G. Vander Heiden, J. W. Locasale, K. D. Swanson et al., “Evidence for an alternative glycolytic pathway in rapidly proliferating cells,” Science, vol. 329, no. 5998, pp. 1492–1499, 2010. View at Publisher · View at Google Scholar
  107. R. J. DeBerardinis, A. Mancuso, E. Daikhin et al., “Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19345–19350, 2007. View at Publisher · View at Google Scholar
  108. D. R. Wise, R. J. Deberardinis, A. Mancuso et al., “Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 48, pp. 18782–18787, 2008. View at Publisher · View at Google Scholar · View at Scopus
  109. R. J. DeBerardinis, J. J. Lum, G. Hatzivassiliou, and C. B. Thompson, “The biology of cancer: metabolic reprogramming fuels cell growth and proliferation,” Cell Metabolism, vol. 7, no. 1, pp. 11–20, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. R. Taub, I. Kirsch, C. Morton et al., “Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 79, no. 24, pp. 7837–7841, 1982. View at Google Scholar
  111. M. Schwab, K. Alitalo, K. H. Klempnauer et al., “Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour,” Nature, vol. 305, no. 5931, pp. 245–248, 1983. View at Google Scholar
  112. M. M. Nau, B. J. Brooks, J. Battey et al., “L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer,” Nature, vol. 318, no. 6041, pp. 69–73, 1985. View at Google Scholar
  113. D. E. Jenne, H. Reimann, J.-I. Nezu et al., “Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase,” Nature Genetics, vol. 18, no. 1, pp. 38–43, 1998. View at Publisher · View at Google Scholar
  114. J. Zhou, J. Scholes, and J. T. Hsieh, “Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer,” Journal of Biological Chemistry, vol. 278, no. 9, pp. 6936–6941, 2003. View at Publisher · View at Google Scholar · View at Scopus
  115. C. A. Castaneda, H. Cortes-Funes, H. L. Gomez, and E. M. Ciruelos, “The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer,” Cancer and Metastasis Reviews, vol. 29, no. 4, pp. 751–759, 2010. View at Publisher · View at Google Scholar
  116. P. M. Comoglio, M. F. Di Renzo, and G. Gaudino, “Protein tyrosine kinases associated with human malignancies,” Annals of the New York Academy of Sciences, vol. 511, pp. 256–261, 1987. View at Google Scholar · View at Scopus
  117. I. Hoshino and H. Matsubara, “Recent advances in histone deacetylase targeted cancer therapy,” Surgery Today, vol. 40, no. 9, pp. 809–815, 2010. View at Publisher · View at Google Scholar
  118. G. Rose, S. Dato, K. Altomare et al., “Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly,” Experimental Gerontology, vol. 38, no. 10, pp. 1065–1070, 2003. View at Publisher · View at Google Scholar · View at Scopus
  119. D. Bellizzi, G. Rose, P. Cavalcante et al., “A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages,” Genomics, vol. 85, no. 2, pp. 258–263, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. D. Bellizzi, G. Covello, F. Cianni, Q. Tong, and G. de Benedictis, “Identification of GATA2 and AP-1 activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene,” Molecules and Cells, vol. 28, no. 2, pp. 87–92, 2009. View at Publisher · View at Google Scholar · View at Scopus
  121. F. Lescai, H. Blanché, A. Nebel et al., “Human longevity and 11p15.5: a study in 1321 centenarians,” European Journal of Human Genetics, vol. 17, no. 11, pp. 1515–1519, 2009. View at Publisher · View at Google Scholar · View at Scopus