Advertisement

Mitochondria and Sex-Specific Cardiac Function

  • Rosa Vona
  • Barbara Ascione
  • Walter Malorni
  • Elisabetta Straface
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1065)

Abstract

The focus of this chapter is the gender differences in mitochondria in cardiovascular disease. There is broad evidence suggesting that some of the gender differences in cardiovascular outcome may be partially related to differences in mitochondrial biology (Ventura–Clapier R, Moulin M, Piquereau J, Lemaire C, Mericskay M, Veksler V, Garnier A, Clin Sci (Lond) 131(9):803–822, 2017)). Mitochondrial disorders are causally affected by mutations in either nuclear or mitochondrial genes involved in the synthesis of respiratory chain subunits or in their posttranslational control. This can be due to mutations of the mtDNA which are transmitted by the mother or mutations in the nuclear DNA. Because natural selection on mitochondria operates only in females, mutations may have had more deleterious effects in males than in females (Ventura–Clapier R, Moulin M, Piquereau J, Lemaire C, Mericskay M, Veksler V, Garnier A, Clin Sci (Lond) 131(9):803–822, 2017; Camara AK, Lesnefsky EJ, Stowe DF. Antioxid Redox Signal 13(3):279–347, 2010). As mitochondrial mutations can affect all tissues, they are responsible for a large panel of pathologies including neuromuscular disorders, encephalopathies, metabolic disorders, cardiomyopathies, neuropathies, renal dysfunction, etc. Many of these pathologies present sex/gender specificity. Thus, alleviating or preventing mitochondrial dysfunction will contribute to mitigating the severity or progression of the development of diseases. Here, we present evidence for the involvement of mitochondria in the sex specificity of cardiovascular disorders.

Keywords

Mitochondrial biology Mutations of mtDNA Mitochondrial dysfunction Krebs cycle Nuclear respiratory factor Apoptotic bodies Redox messenger Reactive oxygen species Calcium overload Heart failure Ischemic preconditioning Autophagy Mitophagy Dynamin Aging heart 

References

  1. 1.
    Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Apoptosis: programmed cell death eliminates unwanted cells. In: Molecular biology of the cell. Garland science, 5th ed. 2008. p. 1115. ISBN:978-0-8153-4105-5.5b.Google Scholar
  2. 2.
    Apostolova N, Blas-Garcia A, Esplugues JV. Mitochondria sentencing about cellular life and death: a matter of oxidative stress. Curr Pharm Des. 2011;17:4047–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Arieli Y, Gursahani H, Eaton MM, Hernandez LA, Schaefer S. Gender modulation of Ca2+ uptake in cardiac mitochondria. J Mol Cell Cardiol. 2004;37:507–13.PubMedCrossRefGoogle Scholar
  4. 4.
    Barrett-Connor E. Sex differences in coronary heart disease. Why are women so superior? The 1995 Ancel Keys Lecture. Circulation. 1997;95:252–64.CrossRefPubMedGoogle Scholar
  5. 5.
    Ben-Porath I, Weinberg RA. The signals and pathways activating cellular senescence. Int J Biochem Cell Biol. 2005;37:961–76.PubMedCrossRefGoogle Scholar
  6. 6.
    Bereiter-Hahn J, Voth M. Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. Microsc Res Tech. 1994;27:198–219.PubMedCrossRefGoogle Scholar
  7. 7.
    Bernardi P, Di Lisa F. The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection. J Mol Cell Cardiol. 2015;78:100–6. aPubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Bernardi P, Di Lisa F, Fogolari F, Lippe G. From ATP to PTP and back: a dual function for the mitochondrial ATP synthase. Circ Res. 2015;116:1850–62. bPubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Besik J, Szarszoi O, Kunes J, Netuka I, Maly J, Kolar F, Pirk J, OstÃdal B. Tolerance to acute ischemia in adult male and female spontaneouslyhypertensive rats. Physiol. Res. 2007; 56:267–74.Google Scholar
  10. 10.
    Bossy-Wetzel E, Barsoum MJ, Godzik A, Schwarzenbacher R, Lipton SA. Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr Opin Cell Biol. 2003;15:706–16.PubMedCrossRefGoogle Scholar
  11. 11.
    Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res. 2017;120:1812–24.PubMedCrossRefGoogle Scholar
  12. 12.
    Burova E, Borodkina A, Shatrova A, Nikolsky N. Sublethal oxidative stress induces the premature senescence of human mesenchymal stem cells derived from endometrium. Oxidative Med Cell Longev. 2013:474931.Google Scholar
  13. 13.
    Camara AK, Lesnefsky EJ, Stowe DF. Potential therapeutic benefits of strategies directed to mitochondria. Antioxid Redox Signal. 2010; 13(3):279–347.CrossRefGoogle Scholar
  14. 14.
    Cao DJ, Lavandero S, Hill JA. Parkin gone wild: Unbridled ubiquitination. Circ Res. 2015;117:31–313.CrossRefGoogle Scholar
  15. 15.
    Carvalho FS, Burgeiro A, Garcia R, Moreno AJ, Carvalho RA, Oliveira PJ. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy. Med Res Rev. 2014; 34(1):106–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Chalmers S, Saunter C, Wilson C, Coats P, Girkin JM, McCarron JG. Mitochondrial motility and vascular smooth muscle proliferation. Arterioscler Thromb Vasc Biol. 2012;32:3000–11.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Chan DC. Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol. 2006;22:79–99.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen Y, Dorn GW. PINK1-phosphorylated mitofusin2 is a Parkin receptor for culling damaged mitochondria. Science. 2013;340:471–5.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Chen L, Gong Q, Stice JP, Knowlton AA. Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc Res. 2009b;84:91–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Chen JQ, Cammarata PR, Baines CP, Yager JD. Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta. 2009a;1793:1540–70.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Chen Y, Liu Y, Dorn GW. Mitochondrial fusion is essential for organelle function and cardiac homeostasis. Circ Res. 2011;109:132–1331.CrossRefGoogle Scholar
  22. 22.
    Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48:749–62.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Collins TJ, Berridge MJ, Lipp P, Bootman MD. Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J. 2002;21:1616–27.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Colom B, Oliver J, Roca P, Garcia-Palmer FJ. Caloric restriction and gender modulate cardiac muscle mitochondrial H2O2 production and oxidative damage. Cardiovasc Res. 2007;74:456–65.PubMedCrossRefGoogle Scholar
  25. 25.
    Dai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, Gollahon K, Martin GM, Loeb LA, Ladiges WC, Rabinovitch PS. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation. 2009;119(21):2789–97.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Dai DF, Chen T, Wanagat J, Laflamme M, Marcinek DJ, Emond MJ, Ngo CP, Prolla TA, Rabinovitch PS. Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell. 2010;9(4):536–44.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116:205–19.PubMedCrossRefGoogle Scholar
  28. 28.
    de Brito OM, Scorrano L. An intimate liaison: spatial organization of the endoplasmic reticulum-mitochondria relationship. EMBO J. 2010;29:2715–23.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Delbridge LM, Mellor KM, Taylor DJ, Gottlieb RA. Myocardial autophagic energy stress responses–macroautophagy, mitophagy, and glycophagy. Am J Physiol Heart Circ Physiol. 2015;308(10):H1194–204.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Delettre C, Griffoin J-M, Kaplan J, Dollfus H, Lorenz B, Faivre L, Lenaers G, Belenguer P, Hamel C. Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet. 2001;109:584–91.PubMedCrossRefGoogle Scholar
  31. 31.
    Dorn GW, Scorrano L. Two close, too close: sarcoplasmic reticulum-mitochondrial crosstalk and cardiomyocyte fate. Circ Res. 2010;107:689–99.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Fang L, Moore X-L, Gao X-M, Dart AM, Lim YL, Du X-J. Down-regulation of mitofusin-2 expression in cardiac hypertrophy in vitro and in vivo. Life Sci. 2007;80:2154–60.PubMedCrossRefGoogle Scholar
  33. 33.
    Fang L, Moore XL, Chan W, White DA, Chin-Dusting J, Dart AM. Decreased fibrocyte number is associated with atherosclerotic plaque instability in man. Cardiovasc Res. 2012; 95(1):124–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Finsterer J, Ohnsorge P. Influence of mitochondrion-toxic agents on the cardiovascular system. Regul Toxicol Pharmacol. 2013;67:434–45.PubMedCrossRefGoogle Scholar
  35. 35.
    Fischer F, Hamann A, Osiewacz HD. Mitochondrial quality control: an integrated network of pathways. Trends Biochem Sci. 2012;37:284–92.PubMedCrossRefGoogle Scholar
  36. 36.
    Gandre-Babbe S, van der Bliek AM. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell. 2008;19:2402–12.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Gonzalez Y, Pokrzywinski KL, Rosen ET, Mog S, Aryal B, Chehab LM, Vijay V, Moland CL, Desai VG, Dickey JS, Rao VA. Reproductive hormone levels and differential mitochondria-related oxidative gene expression as potential mechanisms for gender differences in cardiosensitivity to Doxorubicin in tumor-bearing spontaneously hypertensive rats. Cancer Chemother Pharmacol. 2015 Sep;76(3):447–59.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Gottlieb RA, Thomas A. Mitophagy and mitochondrial quality control mechanisms in the heart. Curr Pathobiol Rep. 2017;5(2):161–9.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Green D. Means to an end: apoptosis and other cell death mechanisms. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. 2011. ISBN:978-0-87969-888-1.Google Scholar
  40. 40.
    Greiten LE, Holditch SJ, Arunachalam SP, Miller VM. Should there be sex-specific criteria for the diagnosis and treatment of heart failure? J Cardiovasc Transl Res. 2014;7:139–55.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Gulati M, Shaw LJ, Bairey Merz CN. Myocardial ischemia in women: lessons from the NHLBI WISE study. Clin Cardiol. 2012;35:141–8.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Hall AR, Hausenloy DJ. The shape of things to come: mitochondrial fusion and fission in the adult heart. Cardiovasc Res. 2012;94:391–2.PubMedCrossRefGoogle Scholar
  43. 43.
    Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S, Gustafsson ÅB. Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J Biol Chem. 2012;287(23):19094–104.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Ide T, Tsutsui H, Ohashi N, Hayashidani S, Suematsu N, Tsuchihashi M, et al. Greater oxidative stress in healthy young men compared with premenopausal women. Arterioscler Thromb Vasc Biol. 2002;22:438–42.PubMedCrossRefGoogle Scholar
  45. 45.
    Janakidevi K, Fisher MA, Del Vecchio PJ, Tiruppathi C, Figge J, Malik AB. Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells. Am J Phys Cell Physiol. 1992;263:C1295–301.CrossRefGoogle Scholar
  46. 46.
    Jay DB, Papaharalambus CA, Seidel-Rogol B, Dikalova AE. Lass’egue B, Griendling KK. Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells. Free Radic Biol Med. 2008;45:329–35.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Johnson JL, van Eys GJ, Angelini GD, George SJ. Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein. Arterioscler Thromb Vasc Biol. 2001;21:114–1151.CrossRefGoogle Scholar
  48. 48.
    Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004;117:2805–12.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Kang R, Zeh HJ, Lotze MT, Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 2011;118:571–80.CrossRefGoogle Scholar
  50. 50.
    Kashatus DF, Lim KH, Brady DC, et al. RALA and RALBP1 regulate mitochondrial fission at mitosis. Nat Cell Biol. 2011;13:1108–15.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Keller KM, Howlett SE. Sex differences in the biology and pathology of the aging heart. Can J Cardiol. 2016;32(9):1065–73.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Khalifa AR, Abdel-Rahman EA, Mahmoud AM, Ali MH, Noureldin M, Saber SH, Mohsen M, Ali SS. Sex-specific differences in mitochondria biogenesis, morphology, respiratory function, and ROS homeostasis in young mouse heart and brain. Physiol Rep. 2017;5(6):pii: e13125.CrossRefGoogle Scholar
  53. 53.
    Klinge CM. Estrogenic control of mitochondrial function and biogenesis. J Cell Biochem. 2008;105:1342–51.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Koleini N, Kardami E. Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity. Oncotarget. 2017;8(28):46663–80.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kovacic JC, Moreno P, Hachinski V, Nabel EG, Fuster V. Cellular senescence, vascular disease, and aging: Part 1 of a 2-part review. Circulation. 2011;123(15):1650–60.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Kubli DA, Zhang X, Lee Y, Hanna RA, Quinsay MN, Nguyen CK, Jimenez R, Petrosyan S, Murphy AN, Gustafsson AB. Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem. 2013;288(2):915–26.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Lee Y, Lee HY, Hanna RA, Gustafsson ÅB. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2011;301(5):H1924–31.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Lee Y, Jeong S-Y, Karbowski M, Smith CL, Youle RJ. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Mol Biol Cell. 2004;15:5001–11.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Leinwand LA. Sex is a potent modifier of the cardiovascular system. J Clin Invest. 2003;112:302–4.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Levine B, Kroemer G. Autophagy in aging, disease and death: the true identity of a cell death impostor. Cell Death Differ. 2012;16:1–2.CrossRefGoogle Scholar
  61. 61.
    Limongelli G, Masarone D, Pacileo G. Mitochondrial disease and the heart. Heart. 2017;103:390–8.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14(2):177–85.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Liu Y, Zhou L, Xu HF, Yan L, Ding F, Hao W, Cao JM, Gao X. A preliminary experimental study on the cardiac toxicity of glutamate and the role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor in rats. Chin Med J (Engl). 2013; 126(7):1323–32Google Scholar
  64. 64.
    Llambi F, Green DR. Apoptosis and oncogenesis: give and take in the BCL-2 family. Curr Opin Genet Dev. 2011;21:12–20.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Marsboom G, Toth PT, Ryan JJ, Hong Z, Wu X, Fang Y-H, Thenappan T, Piao L, Zhang HJ, Pogoriler J, Chen Y, Morrow E, Weir EK, Rehman J, Archer SL. Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res. 2012;11:1484–97.CrossRefGoogle Scholar
  66. 66.
    Malorni W, Straface E, Matarrese P, Ascione B, Coinu R, Canu S, Galluzzo P, Marino M, Franconi F. Redox state and gender differences in vascular smooth muscle cells. FEBS Lett. 2008; 582(5):635–42.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Martin-Garrido A, Williams HC, Lee M, Seidel-Rogol B, Ci X, Dong J-T, Lassègue B, Martín AS, Griendling KK. Transforming growth factor β inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated Cyclin D1 downregulation. PLoS One. 2013;e79657:8.Google Scholar
  68. 68.
    Marí M, Morales A, Colell A, García-Ruiz C, Kaplowitz N, Fernández-Checa JC. Mitochondrial glutathione: features, regulation and role in disease. Biochim Biophys Acta. 2013;1830:3317–28.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Meyer JN, Leung MC, Rooney JP, Sendoel A, Hengartner MO, Kisby GE, Bess AS. Mitochondria as a target of environmental toxicants. Toxicol Sci. 2013; 134(1):1–17.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Mehilli J, Ndrepepa G, Kastrati A, Nekolla SG, Markwardt C, Bollwein H, Pache J, Martinoff S, Dirschinger J, Schwaiger M, Sch­mig A. Gender and myocardial salvage after reperfusion treatment in acute myocardial infarction. J Am Coll Cardiol. 2005; 45(6):828–31.PubMedCrossRefGoogle Scholar
  71. 71.
    Milerová M, Drahota Z, Chytilová A, Tauchmannová K, Houštěk J, Ošťádal B. Sex difference in the sensitivity of cardiac mitochondrial permeability transition pore to calcium load. Mol Cell Biochem. 2016;412:147–54.PubMedCrossRefGoogle Scholar
  72. 72.
    Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069–75.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Mizushima N, Noda T, Ohsumi Y. Apg16p is required for the function of the Apg12p–Apg5p conjugate in the yeast autophagy pathway. EMBO J. 1999;18:3888–96.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Miyamoto S, Brown JH. Drp1 and mitochondrial autophagy lend a helping hand in adaptation to pressure overload. Circulation. 2016;133:1225–7.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Morris PD, Robinson T, Channer KS. Reversible heart failure: toxins, tachycardiomyopathy and mitochondrial abnormalities. Postgrad. Med. J. 2012; 88: 706–12.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Moulin M, Piquereau J, Mateo P, Fortin D, Rucker-Martin C, Gressette M, Lefebvre F, Gresikova M, Solgadi A, Veksler V, Garnier A, Ventura-Clapier R. Sexual dimorphism of doxorubicin-mediated cardiotoxicity: potential role of energy metabolism remodeling. Circ Heart Fail. 2015; 8(1):98–108.Google Scholar
  77. 77.
    Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8(1):e1000298.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183:795–803.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Ong S-B, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121:2012–22.PubMedCrossRefGoogle Scholar
  80. 80.
    Ostadal B, Netuka I, Maly J, Besik J, Ostadalova I. Gender differences in cardiac ischemic injury and protection–experimental aspects. Exp Biol Med (Maywood). 2009;234:1011–9.CrossRefGoogle Scholar
  81. 81.
    Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol. 2010;191:1141–58.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Palmeira CM, Moreno AJ. Mitochondrial bioenergetics. Methods and protocols. Springer Methods in Molecular Biology. 2012, 810. ISBN:978-1-61779-381-3.Google Scholar
  83. 83.
    Papanicolaou KN, Khairallah RJ, Ngoh GA, Chikando A, Luptak I, O’Shea KM, Riley DD, Lugus JJ, Colucci WS, Ledere WJ, Stanley WC, Walsh K. Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol. 2011;31:1309–28.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Papanicolaou KN, Kikuchi R, Ngoh GA, Coughlan KA, Dominguez I, Stanley WC, Walsh K. Mitofusins 1 and 2 are essential for postnatal metabolic remodeling in heart. Circ Res. 2012; 111(8):1012–26.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Pei H, Yang Y, Zhao H, Li X, Yang D, Li D, Yang Y. The role of mitochondrial functional proteins in ROS production in ischemic heart diseases. Oxidative Med Cell Longev. 2016;2016:5470457.CrossRefGoogle Scholar
  86. 86.
    Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300:1140–2.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Pierdominici M, Ortona E, Franconi F, Caprio M, Straface E, Malorni W. Gender specific aspects of cell death in the cardiovascular system. Curr Pharm Des. 2011;17:1046–55.PubMedCrossRefGoogle Scholar
  88. 88.
    Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, Huynh LH, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F. Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res. 2012;94:408–17.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Powers RW, Majors AK, Lykins DL, Sims CJ, Lain KY, Roberts JM. Plasma homocysteine and malondialdehyde are correlated in an age- and genderspecific manner. Metabolism. 2002;51:1433–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Pukac L, Huangpu J, Karnovsky MJ. Platelet-derived growth factor-BB, insulin-like growth factor-I, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Exp Cell Res. 1998;242:548–60.PubMedCrossRefGoogle Scholar
  91. 91.
    Quinsay MN, Thomas RL, Lee Y, Gustafsson AB. Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy. 2010;6(7):855–62.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Rambold AS, Kostelecky B, Elia N, et al. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci U S A. 2011;108:10190–5.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Regitz-Zagrosek V. Therapeutic implications of the gender-specific aspects of cardiovascular disease. Nat Rev Drug Discov. 2006;5:425–39.PubMedCrossRefGoogle Scholar
  94. 94.
    Regitz-Zagrosek V. Sex and gender differences in symptoms of myocardial ischaemia. Eur. Heart J. 2011; 32:3064–066.Google Scholar
  95. 95.
    Ren J, Taegtmeyer H. Too much or not enough of a good thing – the Janus faces of autophagy in cardiac fuel and protein homeostasis. J Mol Cell Cardiol. 2015;84:223–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Rockstein M, Brandt KF. Enzyme changes in flight muscle correlated with aging and flight ability in the male housefly. Science. 1963;139:1049–51.PubMedCrossRefGoogle Scholar
  97. 97.
    Rosdah AA, Holien J K, Delbridge LM, Dusting GJ, Lim SY. Mitochondrial fission- a drug target for cytoprotection or cytodestruction? Pharmacol Res Perspect. 2016;4:e00235.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Rossier MF. T channels and steroid biosynthesis: in search of a link with mitochondria. Cell Calcium. 2006;40:155–64.PubMedCrossRefGoogle Scholar
  99. 99.
    Saito T, Sadoshima J. Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart. Circ Res. 2015;116(8):1477–90.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Salabei JK, Hill BG. Mitochondrial fission induced by platelet-derived growth factor regulates vascular smooth muscle cell bioenergetics and cell proliferation. Redox Biol. 2013;1:542–51.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT. Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci. 2003;116:2763–74.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Scorrano L. Keeping mitochondria in shape: a matter of life and death. Eur J Clin Investig. 2013;43:886–93.CrossRefGoogle Scholar
  103. 103.
    Shafiee H, Mohammadi H, Rezayat SM, Hosseini A, Baeeri M, Hassani S, Mohammadirad A, Bayrami Z, Abdollahi M. Prevention of malathion-induced depletion of cardiac cells mitochondrial energy and free radical damage by a magnetic magnesium-carrying nanoparticle. Toxicol Mech Methods. 2010; 20(9):538–43.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Sharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, Morrow E, Ryan JJ, Archer SL. Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J. 2014;28:316–26.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Shenouda SM, Widlansky ME, Chen K, Xu G, Holbrook M, Tabit CE, Hamburg NM, Frame AA, Caiano TL, Kluge MA, Duess M-A, Levit A, Kim B, Hartman M-L, Joseph L, Shirihai OS, Vita JA. Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus. Circulation. 2011;124:444–53.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Shirakabe A, Ikeda Y, Sciarretta S, Zablocki DK, Sadoshima J. Aging and autophagy in the heart. Circ Res. 2016;118:1563–76.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Simbre VC, Duffy SA, Dadlani GH, Miller TL, Lipshultz SE. Cardiotoxicity of cancer chemotherapy: implications for children. Paediatr Drugs. 2005; 7(3):187–202.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Song Z, Chen H, Fiket M, Alexander C, Chan DC. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol. 2007;178:749–55.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Song M, Gong G, Burelle Y, Gustafsson AB, Kitsis RN, Matkovich SJ, Dorn GW. Interdependence of Parkin-mediated mitophagy and mitochondrial fission in adult mouse hearts. Circ Res. 2015;117:346–51.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Straface E, Vona R, Gambardella L, Ascione B, Marino M, Bulzomi P, Canu S, Coinu R, Rosano G, Malorni W, Franconi F. Cell sex determines anoikis resistance in vascular smooth muscle cells. FEBS Lett. 2009; 583(21):3448–54.PubMedCrossRefGoogle Scholar
  111. 111.
    Straface E, Vona R, Campesi I, Franconi F. Mitochondria can orchestrate sex differences in cell fate of vascular smooth muscle cells from rats. Biol Sex Differ. 2015;16:6–34.Google Scholar
  112. 112.
    Stěrba M, Popelová O, Lenčo J, Fučíková A, Brčáková E, Mazurová Y, Jirkovský E, Simůnek T, Adamcová M, Mičuda S, Stulík J, Geršl V. Proteomic insights into chronic anthracycline cardiotoxicity. J Mol Cell Cardiol. 2011;50(5):849–62.PubMedCrossRefGoogle Scholar
  113. 113.
    Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell. 2016;61:654–66.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Tanaka A, Cleland MM, Xu S, Narendra DP, Suen DF, Karbowski M, Youle RJ. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191:1367–80.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Tokarska-Schlattner M, Zaugg M, Zuppinger C, Wallimann T, Schlattner U. New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics. J Mol Cell Cardiol. 2006;41:389–405.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS. Mitochondrial dysfunction in cardiac aging. Biochim Biophys Acta. 2015;1847(11):1424–33.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Torrealba N, Aranguiz P, Alonso C, Rothermel BA, Lavandero S. Mitochondria in structural and functional cardiac remodeling. Adv Exp Med Biol. 2017;982:277–306.PubMedCrossRefGoogle Scholar
  118. 118.
    Twig G, Elorza A, Molina AJ, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27:433–46.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Twig G, Shirihai OS. The interplay between mitochondrial dynamics and mitophagy. Antioxid Redox Signal. 2011;14:1939–51.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Vásquez-Trincado C, García-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, Lavandero S. Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol. 2016;594(3):509–25.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Velarde MC. Mitochondrial and sex steroid hormone crosstalk during aging. Longev Healthspan. 2014;3:2.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis. The central role of PGC-1α. Cardiovasc Res. 2008;79:208–17.PubMedCrossRefGoogle Scholar
  123. 123.
    Ventura-Clapier R, Moulin M, Piquereau J, Lemaire C, Mericskay M, Veksler V, Garnier A. Mitochondria: a central target for sex differences in pathologies. Clin Sci (Lond). 2017;131(9):803–22.CrossRefGoogle Scholar
  124. 124.
    Viña J, Borrás C, Gambini J, Sastre J, Pallardó FV. Why females live longer than males: control of longevity by sex hormones. Sci Aging Knowl Environ. 2005;2005:pe17.CrossRefGoogle Scholar
  125. 125.
    Watanabe T, Saotome M, Nobuhara M, Sakamoto A, Urushida T, Katoh H, Satoh H, Funaki M, Hayashi H. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance. Exp Cell Res. 2014;323:314–25.PubMedCrossRefGoogle Scholar
  126. 126.
    Witt H, Schubert C, Jaekel J, Fliegner D, Penkalla A, Tiemann K, Stypmann J, Roepcke S, Brokat S, Mahmoodzadeh S, Brozova E, Davidson MM, Ruiz Noppinger P, Grohé C, Regitz-Zagrosek V. Sex-specific pathways in early cardiac response to pressure overload in mice. J Mol Med. 2008;86:1013–24.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Yin Z, Pascual C, Klionsky DJ. Autophagy: machinery and regulation. Microb Cell. 2016;3:588–96.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Youle RJ, Karbowski M. Mitochondrial fission in apoptosis. Nat Rev Mol Cell Biol. 2005;6:657–63.PubMedCrossRefGoogle Scholar
  129. 129.
    Zhivotovsky B. Caspases: the enzymes of death. Essays Biochem. 2003;39:25–40.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Rosa Vona
    • 1
  • Barbara Ascione
    • 1
  • Walter Malorni
    • 1
  • Elisabetta Straface
    • 1
  1. 1.Biomarkers Unit, Center for Gender-Specific Medicine, Istituto Superiore di SanitàRomeItaly

Personalised recommendations