• 1
    Gottlieb, R. A., Burleson, K. O., Kloner, R. A., Babior, B. M., and Engler, R. L. (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J. Clin. Invest. 94, 16211628.
  • 2
    Olivetti, G., Abbi, R., Quaini, F., Kajstura, J., Cheng, W., et al. (1997) Apoptosis in the failing human heart. N Engl. J. Med. 336, 11311141.
  • 3
    Wencker, D., Chandra, M., Nguyen, K., Miao, W., Garantziotis, S., et al. (2003) A mechanistic role for cardiac myocyte apoptosis in heart failure. J. Clin. Invest. 111, 14971504.
  • 4
    Nakayama, H., Chen, X., Baines, C. P., Klevitsky, R., Zhang, X., et al. (2007) Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J. Clin. Invest. 117, 24312444.
  • 5
    Kerr, J. F., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239257.
  • 6
    Gilles, S., Zahler, S., Welsch, U., Sommerhoff, C. P., and Becker, B. F. (2003) Release of TNF-alpha during myocardial reperfusion depends on oxidative stress and is prevented by mast cell stabilizers. Cardiovasc. Res. 60, 608616.
  • 7
    Dörge, H., Schulz, R., Belosjorow, S., Post, H., van de Sand, A., et al. (2002) Coronary microembolization: the role of TNF-alpha in contractile dysfunction. J. Mol. Cell. Cardiol. 34, 5162.
  • 8
    Kubota, T., McTiernan, C. F., Frye, C. S., Slawson, S. E., Lemster, B. H., et al. (1997) Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ. Res. 81, 627635.
  • 9
    Lee, P., Sata, M., Lefer, D. J., Factor, S. M., Walsh, K., et al. (2003) Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo. Am. J. Physiol. Heart Circ. Physiol. 284, H456H463.
  • 10
    Gustafsson, A. B. and Gottlieb, R. A. (2007) Bcl-2 family members and apoptosis, taken to heart. Am. J. Physiol. Cell Physiol. 292, C45C51.
  • 11
    Cheng, E. H., Wei, M. C., Weiler, S., Flavell, R. A., Mak, T. W., et al. (2001) BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell. 8, 705711.
  • 12
    Jiang, X. and Wang, X. (2000) Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J. Biol. Chem. 275, 3119931203.
  • 13
    Li, H., Zhu, H., Xu, C. J., and Yuan, J. (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491501.
  • 14
    Hamacher-Brady, A., Brady, N. R., Logue, S. E., Sayen, M. R., Jinno, M., et al. (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ. 14, 146157.
  • 15
    Toth, A., Jeffers, J. R., Nickson, P., Min, J. Y., Morgan, J. P., et al. (2006) Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol. 291, H52H60.
  • 16
    Hochhauser, E., Kivity, S., Offen, D., Maulik, N., Otani, H., et al. (2003) Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice. Am. J. Physiol. Heart Circ. Physiol. 284, H2351H2359.
  • 17
    Chen, Z., Chua, C. C., Ho, Y. S., Hamdy, R. C., and Chua, B. H. (2001) Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice. Am. J. Physiol. Heart Circ. Physiol. 280, H2313H2320.
  • 18
    Golstein, P. and Kroemer, G. (2007) Cell death by necrosis: towards a molecular definition. Trends Biochem. Sci. 32, 3743.
  • 19
    Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., et al. (2005) Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434, 652658.
  • 20
    Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., et al. (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434, 658662.
  • 21
    Baughman, J. M., Perocchi, F., Girgis, H. S., Plovanich, M., Belcher-Timme, C. A., et al. (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476, 341345.
  • 22
    De Stefani, D., Raffaello, A., Teardo, E., Szabò, I., and Rizzuto, R. (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476, 336340.
  • 23
    García-Rivas, G. de J., Carvajal, K., Correa, F., and Zazueta, C. (2006) Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post-ischaemic functional recovery in rats in vivo. Br. J. Pharmacol. 149, 829837.
  • 24
    Whelan, R. S., Konstantinidis, K., Wei, A. C., Chen, Y., Reyna, D. E., et al. (2012) Bax regulates primary necrosis through mitochondrial dynamics. Proc. Natl. Acad. Sci. USA 109, 65666571.
  • 25
    Oakes, S. A., Opferman, J. T., Pozzan, T., Korsmeyer, S. J., and Scorrano, L. (2003) Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members. Biochem. Pharmacol. 66, 13351340.
  • 26
    Diwan, A., Matkovich, S. J., Yuan, Q., Zhao, W., Yatani, A., et al. (2009) Endoplasmic reticulum-mitochondria crosstalk in NIX-mediated murine cell death. J. Clin. Invest. 119, 203212.
  • 27
    Chen, Y., Lewis, W., Diwan, A., Cheng, E. H., Matkovich, S. J., et al. (2010) Dual autonomous mitochondrial cell death pathways are activated by Nix/BNip3L and induce cardiomyopathy. Proc. Natl. Acad. Sci. USA 107, 90359042.
  • 28
    Cho, Y. S., Challa, S., Moquin D, Genga R, Ray TD., et al. (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137, 11121123.
  • 29
    He, S., Wang, L., Miao, L., Wang, T., Du, F., et al. (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 11001111.
  • 30
    Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., et al. (2011) RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature 471, 368372.
  • 31
    Smith, C. C., Davidson, S. M., Lim, S. Y., Simpkin, J. C., Hothersall, J. S., et al. (2007) Necrostatin: a potentially novel cardioprotective agent? Cardiovasc. Drugs Ther. 21, 227233.
  • 32
    Lim, S. Y., Davidson, S. M., Mocanu, M. M., Yellon, D. M., and Smith, C. C. (2007) The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore. Cardiovasc. Drugs Ther. 21, 467469.
  • 33
    Wang, Z., Jiang, H., Chen, S., Du, F., and Wang, X. (2012) The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148, 228243.
  • 34
    Chen, J. F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., et al. (2008) Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc. Natl. Acad. Sci. USA 105, 21112116.
  • 35
    van Rooij, E., Sutherland, L. B., Liu, N., Williams, A. H., McAnally, J., et al. (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc. Natl. Acad. Sci. USA 103, 1825518260.
  • 36
    Han, M., Toli, J., and Abdellatif, M. (2011) MicroRNAs in the cardiovascular system. Curr. Opin. Cardiol. 26, 181189.
  • 37
    Tang, Y., Zheng, J., Sun, Y., Wu, Z., Liu, Z., et al. (2009) MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2. Int. Heart J. 50, 377387.
  • 38
    Aurora, A. B., Mahmoud, A. I., Luo, X., Johnson, B. A., van Rooij, E., et al. (2012) MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death. J. Clin. Invest. 122, 12221232.
  • 39
    Eulalio, A., Mano, M., Dal Ferro, M., Zentilin, L., Sinagra, G., et al. (2012) Functional screening identifies miRNAs inducing cardiac regeneration. Nature 492, 376381.
  • 40
    Liu, J., van Mil, A., Vrijsen, K., Zhao, J., Gao, L., et al. (2011) MicroRNA-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting RIP1. J. Cell. Mol. Med. 15, 14741482.
  • 41
    Ong, S. B. and Gustafsson, A. B. (2012) New roles for mitochondria in cell death in the reperfused myocardium. Cardiovasc. Res. 94, 190196.
  • 42
    Wakabayashi, J., Zhang, Z., Wakabayashi, N., Tamura, Y., Fukaya, M., et al. (2009) The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186, 805816.
  • 43
    Ong, S. B., Subrayan, S., Lim, S. Y., Yellon, D. M., Davidson, S. M., et al. (2010) Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation 121, 20122022.
  • 44
    Cereghetti, G. M., Stangherlin, A., Martins de Brito, O., Chang, C. R., Blackstone, C., et al. (2008) Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl. Acad. Sci. USA 105, 1580315808.
  • 45
    Wang, J. X., Jiao, J. Q., Li, Q., Long, B., Wang, K., et al. (2011) miR-499 Regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat. Med. 17, 7178.
  • 46
    Piquereau, J., Caffin, F., Novotova, M., Prola, A., Garnier, A., et al. (2012) Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc. Res. 94, 408417.
  • 47
    Chen, L., Liu, T., Tran, A., Lu, X., Tomilov, A. A., et al. (2012) OPA1 mutation and late-onset cardiomyopathy: mitochondrial dysfunction and mtDNA instability. J. Am. Heart Assoc. 1, e003012.
  • 48
    Papanicolaou, K. N., Khairallah, R. J., Ngoh, G. A., Chikando, A., Luptak, I., et al. (2011) Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol. Cell. Biol. 31, 13091328.
  • 49
    Papanicolaou, K. N., Ngoh, G. A., Dabkowski, E. R., O'Connell, K. A., Ribeiro, R. F. Jr., et al. (2012) Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death. Am. J. Physiol. Heart Circ. Physiol. 302, H167H179.
  • 50
    Chung, E. S., Packer, M., Lo, K. H., Fasanmade, A. A., Willerson, J. T., et al. (2003) Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 107, 31333140.