Introduction to Mitochondria in the Heart

  • José Marín-García


In this introductory chapter to Mitochondria Role in Cardiovascular Diseases, we will discuss those primary defects in mitochondrial and nuclear genomes that cause alterations in major aspects of mitochondrial metabolism. They include defects in OXPHOS and TCA cycle activity and regulation, mitochondrial membrane proteins, channels and transporters, transcription, translation and posttranslation modification factors, mitochondrial ribosomal proteins, mtDNA replication and repair, as well as mitochondrial dynamic. How these defects contribute to pathogenesis of cardiovascular diseases will be described in detail later in dedicated chapters.


Mitochondrial Biogenesis Mitochondrial Permeability Transition Pore Mitochondrial Permeability Transition Pore Adenine Nucleotide Translocase Cardiac Mitochondrion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Taegtmeyer H. Cardiac metabolism as a target for the treatment of heart failure. Circulation. 2004;110(8):894–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Neubauer S. The failing heart–an engine out of fuel. N Engl J Med. 2007;356(11):1140–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88(1):40–50.PubMedCrossRefGoogle Scholar
  4. 4.
    McMurray JJ, Pfeffer MA. Heart failure. Lancet. 2005;365(9474):1877–89.PubMedCrossRefGoogle Scholar
  5. 5.
    Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539–49.PubMedCrossRefGoogle Scholar
  6. 6.
    Dayer M, Cowie MR. Heart failure: diagnosis and healthcare burden. Clin Med. 2004;4(1):13–8.PubMedGoogle Scholar
  7. 7.
    Scheffler IE. Mitochondria. Chichester: John Wiley & Sons, Ltd.; 1999.CrossRefGoogle Scholar
  8. 8.
    Gray MW, Burger G, Lang BF. Mitochondrial evolution. Science. 1999;283(5407):1476–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Andersson SG, Karlberg O, Canback B, Kurland CG. On the origin of mitochondria: a genomics perspective. Philos Trans R Soc Lond B Biol Sci. 2003;358(1429):165–77. discussion 177–169.PubMedCrossRefGoogle Scholar
  10. 10.
    Tzagoloff A. Mitochondria. New York: Plenum Press; 1982.Google Scholar
  11. 11.
    Sagan L. On the origin of mitosing cells. J Theor Biol. 1967;14(3):255–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Dyall SD, Brown MT, Johnson PJ. Ancient invasions: from endosymbionts to organelles. Science. 2004;304(5668):253–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Embley TM, Martin W. Eukaryotic evolution, changes and challenges. Nature. 2006;440(7084):623–30.PubMedCrossRefGoogle Scholar
  14. 14.
    de Duve C. The origin of eukaryotes: a reappraisal. Nat Rev Genet. 2007;8(5):395–403.PubMedCrossRefGoogle Scholar
  15. 15.
    Gross J, Bhattacharya D. Mitochondrial and plastid evolution in eukaryotes: an outsiders’ perspective. Nat Rev Genet. 2009;10(7):495–505.PubMedCrossRefGoogle Scholar
  16. 16.
    Holland HD. The oxygenation of the atmosphere and oceans. Philos Trans R Soc Lond B Biol Sci. 2006;361(1470):903–15.PubMedCrossRefGoogle Scholar
  17. 17.
    Martin W, Herrmann RG. Gene transfer from organelles to the nucleus: how much, what happens, and Why? Plant Physiol. 1998;118(1):9–17.PubMedCrossRefGoogle Scholar
  18. 18.
    Dimmer KS, Scorrano L. (De)constructing mitochondria: what for? Physiology (Bethesda). 2006;21:233–41.CrossRefGoogle Scholar
  19. 19.
    Liesa M, Palacin M, Zorzano A. Mitochondrial dynamics in mammalian health and disease. Physiol Rev. 2009;89(3):799–845.PubMedCrossRefGoogle Scholar
  20. 20.
    Ong SB, Hausenloy DJ. Mitochondrial morphology and cardiovascular disease. Cardiovasc Res. 2010;88(1):16–29.PubMedCrossRefGoogle Scholar
  21. 21.
    Hoppel CL, Tandler B, Fujioka H, Riva A. Dynamic organization of mitochondria in human heart and in myocardial disease. Int J Biochem Cell Biol. 2009;41(10):1949–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Riva A, Tandler B, Loffredo F, Vazquez E, Hoppel C. Structural differences in two biochemically defined populations of cardiac mitochondria. Am J Physiol Heart Circ Physiol. 2005;289(2):H868–72.PubMedCrossRefGoogle Scholar
  23. 23.
    Blachly-Dyson E, Forte M. VDAC channels. IUBMB Life. 2001;52(3–5):113–8.PubMedGoogle Scholar
  24. 24.
    Rostovtseva TK, Tan W, Colombini M. On the role of VDAC in apoptosis: fact and fiction. J Bioenerg Biomembr. 2005;37(3):129–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion–a target for cardioprotection. Cardiovasc Res. 2004;61(3):372–85.PubMedCrossRefGoogle Scholar
  26. 26.
    Di Lisa F, Canton M, Menabo R, Kaludercic N, Bernardi P. Mitochondria and cardioprotection. Heart Fail Rev. 2007;12(3–4):249–60.PubMedCrossRefGoogle Scholar
  27. 27.
    Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007;87(1):99–163.PubMedCrossRefGoogle Scholar
  28. 28.
    Baines CP. The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol. 2009;46(6):850–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol. 1974;36:413–59.PubMedCrossRefGoogle Scholar
  30. 30.
    Ashrafian H, Frenneaux MP. Metabolic modulation in heart failure: the coming of age. Cardiovasc Drugs Ther. 2007;21(1):5–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Bessman SP, Geiger PJ. Transport of energy in muscle: the phosphorylcreatine shuttle. Science. 1981;211(4481):448–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J. 1992;281(Pt 1):21–40.PubMedGoogle Scholar
  33. 33.
    Ingwall JS. ATP and the heart. Norwell, MA: Kluwer; 2002.CrossRefGoogle Scholar
  34. 34.
    Guimbal C, Kilimann MW. A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. J Biol Chem. 1993;268(12):8418–21.PubMedGoogle Scholar
  35. 35.
    Lopaschuk GD, Collins-Nakai RL, Itoi T. Developmental changes in energy substrate use by the heart. Cardiovasc Res. 1992;26(12):1172–80.PubMedCrossRefGoogle Scholar
  36. 36.
    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483–95.PubMedCrossRefGoogle Scholar
  37. 37.
    Di Lisa F, Bernardi P. Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition. Cardiovasc Res. 2005;66(2):222–32.PubMedCrossRefGoogle Scholar
  38. 38.
    Pi Y, Goldenthal MJ, Marin-Garcia J. Mitochondrial channelopathies in aging. J Mol Med. 2007;85(9):937–51.PubMedCrossRefGoogle Scholar
  39. 39.
    Druzhyna NM, Wilson GL, LeDoux SP. Mitochondrial DNA repair in aging and disease. Mech Ageing Dev. 2008;129(7–8):383–90.PubMedCrossRefGoogle Scholar
  40. 40.
    Lesnefsky EJ, Hoppel CL. Oxidative phosphorylation and aging. Ageing Res Rev. 2006;5(4):402–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Paradies G, Ruggiero FM. Age-related changes in the activity of the pyruvate carrier and in the lipid composition in rat-heart mitochondria. Biochim Biophys Acta. 1990;1016(2):207–12.PubMedCrossRefGoogle Scholar
  42. 42.
    McMillin JB, Taffet GE, Taegtmeyer H, Hudson EK, Tate CA. Mitochondrial metabolism and substrate competition in the aging Fischer rat heart. Cardiovasc Res. 1993;27(12):2222–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Zinser E, Sperka-Gottlieb CD, Fasch EV, Kohlwein SD, Paltauf F, Daum G. Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae. J Bacteriol. 1991;173(6):2026–34.PubMedGoogle Scholar
  44. 44.
    Schlame M. Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes. J Lipid Res. 2008;49(8):1607–20.PubMedCrossRefGoogle Scholar
  45. 45.
    Joshi AS, Zhou J, Gohil VM, Chen S, Greenberg ML. Cellular functions of cardiolipin in yeast. Biochim Biophys Acta. 2009;1793(1):212–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Sparagna GC, Lesnefsky EJ. Cardiolipin remodeling in the heart. J Cardiovasc Pharmacol. 2009;53(4):290–301.PubMedCrossRefGoogle Scholar
  47. 47.
    Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN. Composition and dynamics of human mitochondrial nucleoids. Mol Biol Cell. 2003;14(4):1583–96.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen XJ, Butow RA. The organization and inheritance of the mitochondrial genome. Nat Rev Genet. 2005;6(11):815–25.PubMedCrossRefGoogle Scholar
  49. 49.
    Malka F, Lombes A, Rojo M. Organization, dynamics and transmission of mitochondrial DNA: focus on vertebrate nucleoids. Biochim Biophys Acta. 2006;1763(5–6):463–72.PubMedCrossRefGoogle Scholar
  50. 50.
    Mootha VK, Bunkenborg J, Olsen JV, et al. Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell. 2003;115(5):629–40.PubMedCrossRefGoogle Scholar
  51. 51.
    Hock MB, Kralli A. Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol. 2009;71:177–203.PubMedCrossRefGoogle Scholar
  52. 52.
    Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008;88(2):611–38.PubMedCrossRefGoogle Scholar
  53. 53.
    Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004;18(4):357–68.PubMedCrossRefGoogle Scholar
  54. 54.
    Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res. 2004;95(6):568–78.PubMedCrossRefGoogle Scholar
  55. 55.
    Dufour CR, Wilson BJ, Huss JM, et al. Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma. Cell Metab. 2007;5(5):345–56.PubMedCrossRefGoogle Scholar
  56. 56.
    Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000;106(7):847–56.PubMedCrossRefGoogle Scholar
  57. 57.
    Garnier A, Fortin D, Delomenie C, Momken I, Veksler V, Ventura-Clapier R. Depressed mitochondrial transcription factors and ­oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003;551(Pt 2):491–501.PubMedCrossRefGoogle Scholar
  58. 58.
    Twig G, Elorza A, Molina AJ, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27(2):433–46.PubMedCrossRefGoogle Scholar
  59. 59.
    Dagda RK, Cherra 3rd SJ, Kulich SM, Tandon A, Park D, Chu CT. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem. 2009;284(20):13843–55.PubMedCrossRefGoogle Scholar
  60. 60.
    Gottlieb RA, Gustafsson AB. Mitochondrial turnover in the heart. Biochim Biophys Acta. 2011;1813(7):1295–301.PubMedCrossRefGoogle Scholar
  61. 61.
    Soubannier V, McBride HM. Positioning mitochondrial plasticity within cellular signaling cascades. Biochim Biophys Acta. 2009;1793(1):154–70.PubMedCrossRefGoogle Scholar
  62. 62.
    Hausenloy DJ, Ruiz-Meana M. Not just the powerhouse of the cell: emerging roles for mitochondria in the heart. Cardiovasc Res. 2010;88(1):5–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Cadenas E, Boveris A, Ragan CI, Stoppani AO. Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Arch Biochem Biophys. 1977;180(2):248–57.PubMedCrossRefGoogle Scholar
  64. 64.
    Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29(3–4):222–30.PubMedCrossRefGoogle Scholar
  65. 65.
    Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc). 2005;70(2):200–14.CrossRefGoogle Scholar
  66. 66.
    Rush JD, Koppenol WH. Oxidizing intermediates in the reaction of ferrous EDTA with hydrogen peroxide. Reactions with organic molecules and ferrocytochrome c. J Biol Chem. 1986;261(15):6730–3.PubMedGoogle Scholar
  67. 67.
    Rush JD, Maskos Z, Koppenol WH. Distinction between hydroxyl radical and ferryl species. Methods Enzymol. 1990;186:148–56.PubMedCrossRefGoogle Scholar
  68. 68.
    Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279(6):L1005–28.PubMedGoogle Scholar
  69. 69.
    Stowe DF, Camara AK. Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxid Redox Signal. 2009;11(6):1373–414.PubMedCrossRefGoogle Scholar
  70. 70.
    Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability ­transition in cardiac myocytes. J Exp Med. 2000;192(7):1001–14.PubMedCrossRefGoogle Scholar
  71. 71.
    Brady NR, Hamacher-Brady A, Westerhoff HV, Gottlieb RA. A wave of reactive oxygen species (ROS)-induced ROS release in a sea of excitable mitochondria. Antioxid Redox Signal. 2006;8(9–10):1651–65.PubMedCrossRefGoogle Scholar
  72. 72.
    Regula KM, Ens K, Kirshenbaum LA. Mitochondria-assisted cell suicide: a license to kill. J Mol Cell Cardiol. 2003;35(6):559–67.PubMedCrossRefGoogle Scholar
  73. 73.
    Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116(2):205–19.PubMedCrossRefGoogle Scholar
  74. 74.
    Gustafsson AB, Gottlieb RA. Heart mitochondria: gates of life and death. Cardiovasc Res. 2008;77(2):334–43.PubMedCrossRefGoogle Scholar
  75. 75.
    Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med. 2009;361(16):1570–83.PubMedCrossRefGoogle Scholar
  76. 76.
    Baines CP. The cardiac mitochondrion: nexus of stress. Annu Rev Physiol. 2010;72:61–80.PubMedCrossRefGoogle Scholar
  77. 77.
    Whelan RS, Kaplinskiy V, Kitsis RN. Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol. 2010;72:19–44.PubMedCrossRefGoogle Scholar
  78. 78.
    Weiss JN, Korge P, Honda HM, Ping P. Role of the mitochondrial permeability transition in myocardial disease. Circ Res. 2003;93(4):292–301.PubMedCrossRefGoogle Scholar
  79. 79.
    Halestrap A. Biochemistry: a pore way to die. Nature. 2005;434(7033):578–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Fabiato A. Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985;85(2):247–89.PubMedCrossRefGoogle Scholar
  81. 81.
    Cannell MB, Cheng H, Lederer WJ. The control of calcium release in heart muscle. Science. 1995;268(5213):1045–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Bers DM. Sarcoplasmic reticulum Ca release in intact ventricular myocytes. Front Biosci. 2002;7:d1697–711.PubMedCrossRefGoogle Scholar
  83. 83.
    Bers DM. Cardiac excitation-contraction coupling. Nature. 2002;415(6868):198–205.PubMedCrossRefGoogle Scholar
  84. 84.
    Yang Z, Steele DS. Effects of cytosolic ATP on spontaneous and triggered Ca2+-induced Ca2+ release in permeabilised rat ventricular myocytes. J Physiol. 2000;523(Pt 1):29–44.PubMedCrossRefGoogle Scholar
  85. 85.
    Yang Z, Steele DS. Effects of cytosolic ATP on Ca(2+) sparks and SR Ca(2+) content in permeabilized cardiac myocytes. Circ Res. 2001;89(6):526–33.PubMedCrossRefGoogle Scholar
  86. 86.
    Liu T, O’Rourke B. Regulation of mitochondrial Ca2+ and its effects on energetics and redox balance in normal and failing heart. J Bioenerg Biomembr. 2009;41(2):127–32.PubMedCrossRefGoogle Scholar
  87. 87.
    Lukyanenko V, Chikando A, Lederer WJ. Mitochondria in cardiomyocyte Ca2+ signaling. Int J Biochem Cell Biol. 2009;41(10):1957–71.PubMedCrossRefGoogle Scholar
  88. 88.
    Dorn 2nd GW, Scorrano L. Two close, too close: sarcoplasmic reticulum-mitochondrial crosstalk and cardiomyocyte fate. Circ Res. 2010;107(6):689–99.PubMedCrossRefGoogle Scholar
  89. 89.
    Yamada EW, Huzel NJ. The calcium-binding ATPase inhibitor protein from bovine heart mitochondria. Purification and properties. J Biol Chem. 1988;263(23):11498–503.PubMedGoogle Scholar
  90. 90.
    Territo PR, Mootha VK, French SA, Balaban RS. Ca(2+) activation of heart mitochondrial oxidative phosphorylation: role of the F(0)/F(1)-ATPase. Am J Physiol Cell Physiol. 2000;278(2):C423–35.PubMedGoogle Scholar
  91. 91.
    Moreno-Sanchez R. Contribution of the translocator of adenine nucleotides and the ATP synthase to the control of oxidative phosphorylation and arsenylation in liver mitochondria. J Biol Chem. 1985;260(23):12554–60.PubMedGoogle Scholar
  92. 92.
    Denton RM, McCormack JG. Ca2+ as a second messenger within mitochondria of the heart and other tissues. Annu Rev Physiol. 1990;52:451–66.PubMedCrossRefGoogle Scholar
  93. 93.
    Balaban RS. Cardiac energy metabolism homeostasis: role of ­cytosolic calcium. J Mol Cell Cardiol. 2002;34(10):1259–71.PubMedCrossRefGoogle Scholar
  94. 94.
    Bender E, Kadenbach B. The allosteric ATP-inhibition of ­cytochrome c oxidase activity is reversibly switched on by cAMP-dependent phosphorylation. FEBS Lett. 2000;466(1):130–4.PubMedCrossRefGoogle Scholar
  95. 95.
    Hill MF, Singal PK. Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation. 1997;96(7):2414–20.PubMedCrossRefGoogle Scholar
  96. 96.
    Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B. A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest. 1962;41:1776–804.PubMedCrossRefGoogle Scholar
  97. 97.
    DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC. Mitochondrial myopathies. Ann Neurol. 1985;17(6):521–38.PubMedCrossRefGoogle Scholar
  98. 98.
    Holt IJ, Harding AE, Morgan-Hughes JA. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 1988;331(6158):717–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 1988;242(4884):1427–30.PubMedCrossRefGoogle Scholar
  100. 100.
    Falk MJaS N. Mitochondrial genetic diseases. Curr Opin Pediatr. 2010;22:711–6.CrossRefGoogle Scholar
  101. 101.
    Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF. The epidemiology of mitochondrial disorders–past, present and future. Biochim Biophys Acta. 2004;1659(2–3):115–20.PubMedGoogle Scholar
  102. 102.
    Cree LM, Samuels DC, Chinnery PF. The inheritance of pathogenic mitochondrial DNA mutations. Biochim Biophys Acta. 2009;1792(12):1097–102.PubMedCrossRefGoogle Scholar
  103. 103.
    DiMauro S, Garone C. Historical perspective on mitochondrial medicine. Dev Disabil Res Rev. 2010;16(2):106–13.PubMedCrossRefGoogle Scholar
  104. 104.
    Wallace DC. Bioenergetics and the epigenome: interface between the environment and genes in common diseases. Dev Disabil Res Rev. 2010;16(2):114–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Wong LJ. Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev. 2010;16(2):154–62.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • José Marín-García
    • 1
  1. 1.The Molecular Cardiology and Neuromuscular InstituteHighland ParkUSA

Personalised recommendations