Skip to main content

Advertisement

Log in

Mitochondrial centrality in heart failure

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

A number of observations have shown that mitochondria are at the center of the pathophysiology of the failing heart and mitochondrial-based oxidative stress (OS), myocardial apoptosis, and cardiac bioenergetic dysfunction are implicated in the progression of heart failure (HF), as shown by both clinical studies and animal models. In this manuscript, we review the body of evidence that multiple defects in mitochondria are central and primary to HF progression. In addition, novel approaches to therapeutic targeting of mitochondrial bioenergetic, biogenic, and signaling abnormalities that can impact HF are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Ventura-Clapier R, Garnier A, Veksler V (2004) Energy metabolism in heart failure. J Physiol 555:1–13

    Article  PubMed  CAS  Google Scholar 

  2. Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356:1140–1151

    Article  PubMed  Google Scholar 

  3. van Bilsen M, Smeets PJ, Gilde AJ, van der Vusse GJ (2004) Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc Res 61:218–226

    Article  PubMed  Google Scholar 

  4. Katz AM (2004) Is the failing heart energy depleted? Cardiol Clin 16:633–644

    Article  Google Scholar 

  5. Ingwall JS, Weiss RG (2004) Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 95:135–145

    Article  PubMed  CAS  Google Scholar 

  6. Weiss JN, Lamp ST (1989) Cardiac ATP-sensitive K+ channels: evidence for preferential regulation by glycolysis. J Gen Physiol 94:911–935

    Article  PubMed  CAS  Google Scholar 

  7. Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280:1763–1766

    Article  PubMed  CAS  Google Scholar 

  8. Bittl JA, Ingwall JS (1985) Reaction rates of creatine kinase and ATP synthesis in the isolated rat heart. A 31P NMR magnetization transfer study. J Biol Chem 260:3512–3517

    PubMed  CAS  Google Scholar 

  9. Jarreta D, Orus J, Barrientos A, Miro O, Roig E, Heras M, Moraes CT, Cardellach F, Casademont J (2000) Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy. Cardiovasc Res 45:860–865

    Article  PubMed  CAS  Google Scholar 

  10. Marin-Garcia J, Goldenthal MJ, Pierpont ME, Ananthakrishnan R (1995) Impaired mitochondrial function in idiopathic dilated cardiomyopathy: biochemical and molecular analysis. J Card Fail 1:285–291

    Article  PubMed  CAS  Google Scholar 

  11. Quigley AF, Kapsa RM, Esmore D, Hale G, Byrne E (2000) Mitochondrial respiratory chain activity in idiopathic dilated cardiomyopathy. J Card Fail 6:47–55

    Article  PubMed  CAS  Google Scholar 

  12. Ingwall JS, Atkinson DE, Clarke K, Fetters JK (1990) Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. Eur Heart J 11:108–115

    PubMed  CAS  Google Scholar 

  13. Starling RC, Hammer DF, Altschuld RA (1998) Human myocardial ATP content and in vivo contractile function. Molec Cell Biochem 180:171–177

    Article  PubMed  CAS  Google Scholar 

  14. Beer M, Seyfarth T, Sandstede J, Landschutz W, Lipke C, Kostler H, von Kienlin M, Harre K, Hahn D, Neubauer S (2002) Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol 40:1267–1274

    Article  PubMed  CAS  Google Scholar 

  15. Shen W, Asai K, Uechi M, Mathier MA, Shannon RP, Vatner SF, Ingwall JS (1999) Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs: a compensatory role for the parallel loss of creatine. Circulation 100:2113–2118

    PubMed  CAS  Google Scholar 

  16. Tian R, Ingwall JS (1999) The molecular energetics of the failing heart from animal models—small animal models. Heart Failure Rev 4:235–253

    Article  Google Scholar 

  17. Zhang J, Bache RJ (1999) The molecular energetics of the failing heart from animal models—large animal models. Heart Failure Rev 4:255–267

    Article  CAS  Google Scholar 

  18. Nakae I, Mitsunami K, Omura T, Yabe T, Tsutamoto T, Matsuo S, Takahashi M, Morikawa S, Inubushi T, Nakamura Y, Kinoshita M, Horie M (2003) Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy. J Am Coll Cardiol 42:1587–1593

    Article  PubMed  CAS  Google Scholar 

  19. Hardy CJ Weiss RG, Bottomley PA, Gerstenblith G (1991) Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy. Am Heart J 122:795–801

    Article  Google Scholar 

  20. Neubauer S, Horn M, Cramer M, Harre K, Newell JB, Peters W, Pabst T, Ertl G, Hahn D, Ingwall JS, Kochsiek K (1997) Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96:2190–2196

    PubMed  CAS  Google Scholar 

  21. Neubauer S, Remkes H, Spindler M, Horn M, Weismann F, Prestle J, Walzel B, Ertl G, Hasenfuss G, Wallimann T (1999) Down regulation of the Na(+)-creatine co-transporter in failing human myocardium and in experimental heart failure. Circulation 100:1847–1850

    PubMed  CAS  Google Scholar 

  22. Saupe KW, Spindler M, Hopkins JC, Shen W, Ingwall JS (2000) Kinetic, thermodynamic, and developmental consequences of deleting creatine kinase isoenzymes from the heart. Reaction kinetics of the creatine kinase isoenzymes in the intact heart. J Biol Chem 275:19742–19746

    Article  PubMed  CAS  Google Scholar 

  23. Esposito LA, Melov S, Panov A, Cottrell BA, Wallace DC (1999) Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci USA 96:4820–4825

    Article  PubMed  CAS  Google Scholar 

  24. Graham BH, Waymire KG, Cottrell B, Trounce IA, MacGregor GR, Wallace DC (1997) A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator. Nat Genet 16:226–234

    Article  PubMed  CAS  Google Scholar 

  25. Nahrendorf M, Spindler M, Hu K, Bauer L, Ritter O, Nordbeck P, Quaschning T, Hiller KH, Wallis J, Ertl G, Bauer WR, Neubauer S (2005) Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction. Cardiovasc Res 65:419–427

    Article  PubMed  CAS  Google Scholar 

  26. De Sousa E, Veksler V, Minajeva A, Kaasik A, Mateo P, Mayoux E, Hoerter J, Bigard X, Serrurier B, Ventura-Clapier R (1999) Subcellular creatine kinase alterations—implications in heart failure. Circ Res 85:68–76

    PubMed  Google Scholar 

  27. Palmieri L, Alberio S, Pisano I, Lodi T, Meznaric-Petrusa M, Zidar J, Santoro A, Scarcia P, Fontanesi F, Lamantea E, Ferrero I, Zeviani M (2005) Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum Mol Genet 14:3079–3088

    Article  PubMed  CAS  Google Scholar 

  28. Marín-García J, Goldenthal MJ (2002) Understanding the impact of mitochondrial defects in cardiovascular disease: a review. J Card Fail 8:347–361

    Article  PubMed  Google Scholar 

  29. Andreu AL, Checcarelli N, Iwata S, Shanske S, DiMauro S (2000) A missense mutation in the mitochondrial cytochrome b gene in a revisited case with histiocytoid cardiomyopathy. Pediatr Res 48:311–314

    Article  PubMed  CAS  Google Scholar 

  30. Pastores GM, Santorelli FM, Shanske S, Gelb BD, Fyfe B, Wolfe D, Willner JP (1994) Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G). Am J Med Genet 50:265–271

    Article  PubMed  CAS  Google Scholar 

  31. Jonckheere A, Hogeveen M, Nijtmans L, van den Brand M, Janssen A, Diepstra H, van den Brandt F, van den Heuvel L, Hol F, Hofste T, Kapusta L, Dillmann U, Shamdeen M, Smeitink J, Rodenburg R (2007) A novel mitochondrial ATP8 (MT-ATP8) gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy. J Med Genet [Epub ahead of print]

  32. Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A (2001) Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88:529–535

    PubMed  CAS  Google Scholar 

  33. Ide T, Tsutsui H, Kinugawa S, Utsumi H, Kang D, Hattori N, Uchida K, Arimura K, Egashira K, Takeshita A (1999) Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium. Circ Res 85:357–363

    PubMed  CAS  Google Scholar 

  34. Ide T, Tsutsui H, Kinugawa S, Suematsu N, Hayashidani S, Ichikawa K, Utsumi H, Machida Y, Egashira K, Takeshita A (2000) Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. Circ Res 86:152–157

    PubMed  CAS  Google Scholar 

  35. Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115:500–508

    Article  PubMed  CAS  Google Scholar 

  36. Cesselli D, Jakoniuk I, Barlucchi L, Beltrami AP, Hintze TH, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2001) Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circ Res 89:279–286

    Article  PubMed  CAS  Google Scholar 

  37. Marin-Garcia J, Goldenthal MJ, Moe GW (2001) Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure. Cardiovasc Res 52:103–110

    Article  PubMed  CAS  Google Scholar 

  38. Nordberg J, Arner ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31:1287–1312

    Article  PubMed  CAS  Google Scholar 

  39. Nojiri H, Shimizu T, Funakoshi M, Yamaguchi O, Zhou H, Kawakami S, Ohta Y, Sami M, Tachibana T, Ishikawa H, Kurosawa H, Kahn RC, Otsu K, Shirasawa T (2006) Oxidative stress causes heart failure with impaired mitochondrial respiration. J Biol Chem 281:33789–33801

    Article  PubMed  CAS  Google Scholar 

  40. Huang TT, Carlson EJ, Kozy HM, Mantha S, Goodman SI, Ursell PC, Epstein CJ (2001) Genetic modification of prenatal lethality and dilated cardiomyopathy in Mn superoxide dismutase mutant mice. Free Radic Biol Med 31:1101–1110

    Article  PubMed  CAS  Google Scholar 

  41. Conrad M, Jakupoglu C, Moreno SG, Lippl S, Banjac A, Schneider M, Beck H, Hatzopoulos AK, Just U, Sinowatz F, Schmahl W, Chien KR, Wurst W, Bornkamm GW, Brielmeier M (2004) Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol 24:9414–9423

    Article  PubMed  CAS  Google Scholar 

  42. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11:376–381

    Article  PubMed  CAS  Google Scholar 

  43. Shiomi T, Tsutsui H, Matsusaka H, Murakami K, Hayashidani S, Ikeuchi M, Wen J, Kubota T, Utsumi H, Takeshita A (2004) Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 109:544–549

    Article  PubMed  CAS  Google Scholar 

  44. 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 308:1909–1911

    Article  PubMed  CAS  Google Scholar 

  45. Mak S, Newton GE (2001) The oxidative stress hypothesis of congestive heart failure radical thoughts. Chest 120:2035–2046

    Article  PubMed  CAS  Google Scholar 

  46. Sam F, Kerstetter DL, Pimental DR, Mulukutla S, Tabaee A, Bristow MR, Colucci WS, Sawyer DB (2005) Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium. J Card Fail 11:473–480

    Article  PubMed  CAS  Google Scholar 

  47. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, Schmidt U, Semigran MJ, Dec GW, Khaw BA (1996) Apoptosis in myocytes in end-stage heart failure. N Engl J Med 35:1182–1189

    Article  Google Scholar 

  48. Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Di Loreto C, Beltrami CA, Krajewski S, Reed JC, Anversa P (1997) Apoptosis in the failing heart. N Engl J Med 336:1131–1141

    Article  PubMed  CAS  Google Scholar 

  49. Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    Article  PubMed  CAS  Google Scholar 

  50. Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99

    Article  PubMed  CAS  Google Scholar 

  51. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446

    Article  PubMed  CAS  Google Scholar 

  52. 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 86:147–157

    Article  PubMed  CAS  Google Scholar 

  53. Kroemer G (2003) Mitochondrial control of apoptosis: an introduction. Biochem Biophys Res Commun 304:433–435

    Article  PubMed  CAS  Google Scholar 

  54. Marzo I, Brenner C, Zamzami N, Susin SA, Beutner G, Brdiczka D, Remy R, Xie ZH, Reed JC, Kroemer G (1998) The permeability transition pore complex: a target for apoptosis regulation by caspases and Bcl-2 related proteins. J Exp Med 187:1261–1267

    Article  PubMed  CAS  Google Scholar 

  55. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes S, Mannella CA, Korsmeyer SJ (2002) A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. Dev Cell 2:55–67

    Article  PubMed  CAS  Google Scholar 

  56. Neuse M, Monticone R, Lundberg MS, Chesley AT, Fleck E, Crow MT (2001) The apoptotic regulatory protein ARC (apoptosis repressor with caspase recruitment domain) prevents oxidant stress-mediated cell death by preserving mitochondrial function. J Biol Chem 276:33915–33922

    Article  Google Scholar 

  57. Pi Y, Goldenthal MJ, Marín-García J (2007) Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury. Mol Cell Biochem 301:181–189

    Article  PubMed  CAS  Google Scholar 

  58. Akyurek O, Akyurek N, Sayin T, Dincer I, Berkalp B, Akyol G, Ozenci M, Oral D (2001) Association between the severity of heart failure and the susceptibility of myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy. Int J Cardiol 80:29–36

    Article  PubMed  CAS  Google Scholar 

  59. Kirshenbaum LA, de Moissac D (1997) The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation 96:1580–1585

    PubMed  CAS  Google Scholar 

  60. Zhu L, Yu Y, Chua BH, Ho YS, Kuo TH (2001) Regulation of sodium-calcium exchange and mitochondrial energetics by Bcl-2 in the heart of transgenic mice. J Mol Cell Cardiol 33:2135–2144

    Article  PubMed  CAS  Google Scholar 

  61. Kang PM, Haunstetter A, Aoki H, Usheva A, Izumo S (2000) Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation. Circ Res 87:118–125

    PubMed  CAS  Google Scholar 

  62. Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y (2000) Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J Cell Biol 150:1283–1298

    Article  PubMed  CAS  Google Scholar 

  63. Linden M, Li Z, Paulin D, Gotow T, Leterrier JF (2001) Effects of desmin gene knockout on mice heart mitochondria. J Bioenerg Biomembr 33:333–341

    Article  PubMed  CAS  Google Scholar 

  64. Weisleder N, Taffet GE, Capetanaki Y (2004) Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc Natl Acad Sci USA 101:769–774

    Article  PubMed  CAS  Google Scholar 

  65. Imahashi K, Schneider MD, Steenbergen C, Murphy E (2004) Transgenic expression of Bcl-2 modulates energy metabolism, prevents cytosolic acidification during ischemia, and reduces ischemia/reperfusion injury. Circ Res 95:734–741

    Article  PubMed  CAS  Google Scholar 

  66. Vahsen N, Cande C, Briere JJ, Benit P, Joza N, Larochette N, Mastroberardino PG, Pequignot MO, Casares N, Lazar V, Feraud O, Debili N, Wissing S, Engelhardt S, Madeo F, Piacentini M, Penninger JM, Schagger H, Rustin P, Kroemer G (2004) AIF deficiency compromises oxidative phosphorylation. EMBO J 23:4679–4689

    Article  PubMed  CAS  Google Scholar 

  67. Joza N, Oudit GY, Brown D, Benit P, Kassiri Z, Vahsen N, Benoit L, Patel MM, Nowikovsky K, Vassault A, Backx PH, Wada T, Kroemer G, Rustin P, Penninger JM (2005) Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy. Mol Cell Biol 25:10261–10272

    Article  PubMed  CAS  Google Scholar 

  68. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P (1996) Apoptotic and necrotic myocyte cell death are independent contributing variables of infarct size in rats. Lab Invest 74:86–107

    PubMed  CAS  Google Scholar 

  69. Rayment NB, Haven AJ, Madden B, Murday A, Trickey R, Shipley M, Davies M J, Katz DR (1999) Myocyte loss in chronic heart failure. J Pathol 188:213–219

    Article  PubMed  CAS  Google Scholar 

  70. Gill C, Mestril R, Samali A (2002) Losing heart: the role of apoptosis in heart disease–a novel therapeutic target? FASEB J 16:135–146

    Article  PubMed  CAS  Google Scholar 

  71. Honda O, Kuroda M, Joja I, Asaumi J, Takeda Y, Akaki S, Togami I, Kanazawa S, Kawasaki S, Hiraki Y (2000) Assessment of secondary necrosis of Jurkat cells using a new microscopic system and double staining method with annexin V and propidium iodide. Int J Oncol 16:283–288

    PubMed  CAS  Google Scholar 

  72. Malhi H, Gores GJ, Lemasters JJ (2006) Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology 43:S31–S44

    Article  PubMed  CAS  Google Scholar 

  73. Kim JS, He L, Lemasters JJ (2003) Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 304:463–470

    Article  PubMed  CAS  Google Scholar 

  74. Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA, Herman B (1998) The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta 1366:177–196

    Article  PubMed  CAS  Google Scholar 

  75. Zamzami N, Hirsch T, Dallaporta B, Petit PX, Kroemer G (1997) Mitochondrial implication in accidental and programmed cell death: apoptosis and necrosis. J Bioenerg Biomembr 29:185–213

    Article  PubMed  CAS  Google Scholar 

  76. Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Zhang H, Jaleel N, Chua BH, Hewett TE, Robbins J, Houser SR, Molkentin JD (2007) Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest 117:2431–2444

    Article  PubMed  CAS  Google Scholar 

  77. Knaapen MW, Davies MJ, De Bie M., Haven AJ, Martinet W, Kockx MM (2001) Apoptotic versus autophagic cell death in heart failure. Cardiovasc Res 51:304–312

    Article  PubMed  CAS  Google Scholar 

  78. Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict? J Clin Invest 115:2679–2688

    Article  PubMed  CAS  Google Scholar 

  79. Scherz-Shouval R, Elazar Z (2007) ROS, mitochondria and the regulation of autophagy. Trends Cell Biol 17:422–427

    Article  PubMed  CAS  Google Scholar 

  80. Attardi G, Schatz G (1988) Biogenesis of mitochondria. Annu Rev Cell Biol 4:289–333

    Article  PubMed  CAS  Google Scholar 

  81. Ryan MT, Hoogenraad NJ (2007) Mitochondrial-nuclear communications. Annu Rev Biochem 76:701–726

    Article  PubMed  CAS  Google Scholar 

  82. Parisi MA, Clayton DA (1991) Similarity of human mitochondrial transcription factor 1 to high mobility group proteins. Science 252:965–969

    Article  PubMed  CAS  Google Scholar 

  83. Scarpulla RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576:1–14

    PubMed  CAS  Google Scholar 

  84. Huss JM, Kelly DP (2004) Nuclear receptor signaling and cardiac energetics. Circ Res 95:568–578

    Article  PubMed  CAS  Google Scholar 

  85. Wu ZD, Puigserver P, Andersson U, Zhang CY, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124

    Article  PubMed  CAS  Google Scholar 

  86. Garnier A, Fortin D, Delomenie C, Momken I, Veksler V, Ventura-Clapier R (2003) Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol 551:491–501

    Article  PubMed  CAS  Google Scholar 

  87. Lewis W, Day BJ, Kohler JJ, Hosseini SH, Chan SS, Green EC, Haase CP, Keebaugh ES, Long R, Ludaway T, Russ R, Steltzer J, Tioleco N, Santoianni R, Copeland WC (2007) Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase gamma. Lab Invest 87:326–335

    PubMed  CAS  Google Scholar 

  88. Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS, Clayton DA (1998) Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 18:231–236

    Article  PubMed  CAS  Google Scholar 

  89. Wang J, Wilhelmsson H, Graff C, Li H, Oldfors A, Rustin P, Bruning JC, Kahn CR, Clayton DA, Barsh GS, Thoren P, Larsson NG (1999) Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet 21:133–137

    Article  PubMed  CAS  Google Scholar 

  90. Wang J, Silva JP, Gustafsson CM, Rustin P, Larsson NG (2001) Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression. Proc Natl Acad Sci USA 98:4038–4043

    Article  PubMed  CAS  Google Scholar 

  91. Hansson A. Hance N, Dufour E, Rantanen A, Hultenby K, Clayton DA, Wibom R, Larsson NG (2004) A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient hearts. Proc Natl Acad Sci USA 101:3136–3141

    Article  Google Scholar 

  92. Ikeuchi M, Matsusaka H, Kang D, Matsushima S, Ide T, Kubota T, Fujiwara T, Hamasaki N, Takeshita A, Sunagawa K, Tsutsui H (2005) Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction. Circulation 112:683–690

    Article  PubMed  CAS  Google Scholar 

  93. Bohlega S, Tanji K, Santorelli FM, Hirano M, al-Jishi A, DiMauro S (1996) Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy. Neurology 46:1329–1334

    PubMed  CAS  Google Scholar 

  94. Suomalainen A, Paetau A, Leinonen H, Majander A, Peltonen L, Somer H (1992) Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA. Lancet 340:1319–1320

    Article  PubMed  CAS  Google Scholar 

  95. Kaukonen J, Juselius JK, Tiranti V, Kyttälä A, Zeviani M, Comi GP, Keränen S, Peltonen L, Suomalainen A (2000) Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 289:782–785

    Article  PubMed  CAS  Google Scholar 

  96. Zhang D, Mott JL, Farrar P, Ryerse JS, Chang SW, Stevens M, Denniger G, Zassenhaus HP (2003) Mitochondrial DNA mutations activate the mitochondrial apoptotic pathway and cause dilated cardiomyopathy. Cardiovasc Res 57:147–157

    Article  PubMed  CAS  Google Scholar 

  97. Mott JL, Zhang D, Stevens M, Chang S, Denniger G, Zassenhaus HP (2001) Oxidative stress is not an obligate mediator of disease provoked by mitochondrial DNA mutations. Mutat Res 474:35–45

    PubMed  CAS  Google Scholar 

  98. Zhang D, Mott JL, Chang SW, Stevens M, Mikolajczak P, Zassenhaus HP (2005) Mitochondrial DNA mutations activate programmed cell survival in the mouse heart. Am J Physiol Heart Circ Physiol 288:H2476–H2483

    Article  PubMed  CAS  Google Scholar 

  99. Razeghi P, Young ME, Alcorn JL, Moravec CS, Frazier OH, Taegtmeyer H (2001) Metabolic gene expression in fetal and failing human heart. Circulation 104:2923–2931

    Article  PubMed  CAS  Google Scholar 

  100. Hwang JJ, Allen PD, Tseng GC, Lam CW, Fananapazir L, Dzau VJ, Liew CC (2002) Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics 10:31–44

    PubMed  CAS  Google Scholar 

  101. Gao Z, Xu H, DiSilvestre D, Halperin VL, Tunin R, Tian Y, Yu W, Winslow R, Tomaselli GF (2006) Transcriptomic profiling of the canine tachycardia-induced heart failure model: global comparison to human and murine heart failure. J Mol Cell Cardiol 40:76–86

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José Marín-García.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marín-García, J., Goldenthal, M.J. Mitochondrial centrality in heart failure. Heart Fail Rev 13, 137–150 (2008). https://doi.org/10.1007/s10741-007-9079-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-007-9079-1

Keywords

Navigation