Modulation of Mitochondrial Permeability Transition in Ischemia- Reperfusion Injury of the Heart. Advantages and Limitations

Current Medicinal Chemistry

Volumn 22, Issue 20, 2015, Pages 2480-2487

  Lisa, Fabio Di ^a   Bernardi, Paolo ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

calcium; cyclophilin D; heart; ischemia; Permeability transition; reactive oxygen species

Indexed keywords

CYCLOPHILIN D; CYCLOPHILIN D INHIBITOR; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; MITOCHONDRIAL PERMEABILITY TRANSITION PORE INHIBITOR; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; CARRIER PROTEIN;

ADVERSE OUTCOME; DISORDERS OF MITOCHONDRIAL FUNCTIONS; HEART MUSCLE INJURY; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HUMAN; MITOCHONDRIAL PERMEABILITY; PROTEIN FUNCTION; PROTEIN STRUCTURE; REPERFUSION INJURY; REVIEW; ANIMAL; METABOLISM; MITOCHONDRION;

ANIMALS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MYOCARDIAL ISCHEMIA; MYOCARDIAL REPERFUSION INJURY;

EID: 84938633869     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867322666150530210005     Document Type: Review

References (108)

1. Kaltenbach, J.P.; Jennings, R.B. Metabolism of ischemic cardiac muscle. Circ. Res., 1960, 8, 207-213
2. Jennings, R.B.; Herdson, P.B.; Sommers, H.M. Structural and functional abnormalities in mitochondria isolated from ischemic dog myocardium. Lab. Invest., 1969, 20, 548-557
3. Jennings, R.B.; Herdson, P.B.; Hill, M.L. Pyruvate metabolism in mitochondria isolated from dog myocardium. Lab. Invest., 1969, 20, 537-547
4. Jennings, R.B.; Baum, J.H.; Herdson, P.B. Fine Structural Changes in Myocardial Ischemic Injury. Arch. Pathol., 1965, 79, 135-143
5. Shen, A.C.; Jennings, R.B. Myocardial calcium and magnesium in acute ischemic injury. Am. J. Pathol., 1972, 67, 417-421
6. Wrogemann, K.; Jacobson, B.E.; Blanchaer, M.C. On the mechanism of a calcium-associated defect of oxidative phosphorylation in progessive muscular dystrophy. Arch. Biochem. Biophys., 1973, 159, 267-278
7. Ganote, C.E.; Worstell, J.; Kaltenbach, J.P. Oxygen-induced enzyme release after irreversible myocardial injury. Effects of cyanide in perfused rat hearts. Am. J. Pathol., 1976, 84, 327-350
8. Zamzami, N.; Marchetti, P.; Castedo, M.; Zanin, C.; Vayssiere, J.L.; Petit, P.X.; Kroemer, G. Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J. Exp. Med., 1995, 181, 1661-1672
9. Liu, X.S.; Kim, C.N.; Yang, J.; Jemmerson, R.; Wang, X.D. Induction of apoptotic program in cell free extracts: requirement for dATP and cytochrome c. Cell, 1996, 86, 147-157
10. Hearse, D.J.; Humphrey, S.M.; Bullock, G.R. The oxygen paradox and the calcium paradox: two facets of the same problem. J. Mol. Cell. Cardiol., 1978, 10, 641-668
11. Hunter, D.R.; Haworth, R.A.; Southard, J.H. Relationship between configuration, function, and permeability in calcium-treated mitochondria. J. Biol. Chem., 1976, 251, 5069-5077
12. Hunter, D.R.; Haworth, R.A. The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release. Arch. Biochem. Biophys., 1979, 195, 468-477
13. Haworth, R.A.; Hunter, D.R. The Ca2+-induced membrane transition in mitochondria. II. Nature of the Ca2+ trigger site. Arch. Biochem. Biophys., 1979, 195, 460-467
14. Hunter, D.R.; Haworth, R.A. The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms. Arch. Biochem. Biophys., 1979, 195, 453-459
15. Opie, L.H. Myocardial infarct size. Part 2. Comparison of antiinfarct effects of beta-blockade, glucose-insulin-potassium, nitrates, and hyaluronidase. Am. Heart J., 1980, 100, 531-552
16. Vary, T.C.; Reibel, D.K.; Neely, J.R. Control of energy metabolism of heart muscle. Annu. Rev. Physiol., 1981, 43, 419-430
17. Lopaschuk, G.D. Treating ischemic heart disease by pharmacologically improving cardiac energy metabolism. Am. J. Cardiol., 1998, 82, 14K-17K
18. Ferrari, R.; Di Lisa, F.; Raddino, R.; Visioli, O. The effects of ruthenium red on mitochondrial function during post-ischaemic reperfusion. J. Mol. Cell. Cardiol., 1982, 14, 737-740
19. Stone, D.; Darley-Usmar, V.; Smith, D.R.; O'Leary, V. Hypoxiareoxygenation induced increase in cellular Ca2+ in myocytes and perfused hearts: the role of mitochondria. J. Mol. Cell. Cardiol.,, 1989, 21, 963-973
20. Grover, G.J.; Dzwonczyk, S.; Sleph, P.G. Ruthenium red improves postischemic contractile function in isolated rat hearts. J. Cardiovas. Pharmacol., 1990, 16, 783-789
21. Bernardi, P.; Krauskopf, A.; Basso, E.; Petronilli, V.; Blalchy-Dyson, E.; Di Lisa, F.; Forte, M.A. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J., 2006, 273, 2077-2099
22. Piot, C.; Croisille, P.; Staat, P.; Thibault, H.; Rioufol, G.; Mewton, N.; Elbelghiti, R.; Cung, T.T.; Bonnefoy, E.; Angoulvant, D.; Macia, C.; Raczka, F.; Sportouch, C.; Gahide, G.; Finet, G.; ndre-Fouet, X.; Revel, D.; Kirkorian, G.; Monassier, J.P.; Derumeaux, G.; Ovize, M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N. Engl. J. Med., 2008, 359, 473-481
23. Bernardi, P. The mitochondrial permeability transition pore: a mystery solved? Front. Physiol., 2013, 4, 95
24. Di Lisa, F.; Bernardi, P. Mitochondria and ischemia-reperfusion injury of the heart: Fixing a hole. Cardiovasc. Res., 2006, 70, 191-199
25. Di Lisa, F.; Carpi, A.; Giorgio, V.; Bernardi, P. The mitochondrial permeability transition pore and cyclophilin D in cardioprotection. Biochim. Biophys. Acta, 2011, 1813, 1316-1322
26. Halestrap, A.P.; Pasdois, P. The role of the mitochondrial permeability transition pore in heart disease. Biochim. Biophys. Acta, 2009, 1787, 1402-15
27. Gomez, L.; Li, B.; Mewton, N.; Sanchez, I.; Piot, C.; Elbaz, M.; Ovize, M. Inhibition of mitochondrial permeability transition pore opening: translation to patients. Cardiovasc. Res., 2009, 83, 226-33
28. Hausenloy, D.J.; Ong, S.B.; Yellon, D.M. The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res. Cardiol., 2009, 104, 189-202
29. Zorov, D.B.; Juhaszova, M.; Sollott, S.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev., 2014, 94, 909-950
30. Azzolin, L.; von Stockum, S.; Basso, E.; Petronilli, V.; Forte, M.A.; Bernardi, P. The mitochondrial permeability transition from yeast to mammals. FEBS Lett., 2010, 584, 2504-2509
31. Bernardi, P.; Petronilli, V. The permeability transition pore as a mitochondrial calcium release channel: a critical appraisal. J. Bioenerg. Biomembr., 1996, 28, 131-138
32. Wang, W.; Fang, H.; Groom, L.; Cheng, A.; Zhang, W.; Liu, J.; Wang, X.; Li, K.; Han, P.; Zheng, M.; Yin, J.; Wang, W.; Mattson, M.P.; Kao, J.P.; Lakatta, E.G.; Sheu, S.S.; Ouyang, K.; Chen, J.; Dirksen, R.T.; Cheng, H. Superoxide flashes in single mitochondria. Cell, 2008, 134, 279-290
33. Altschuld, R.A.; Hohl, C.M.; Castillo, L.C.; Garleb, A.A.; Starling, R.C.; Brierley, G.P. Cyclosporin inhibits mitochondrial calcium efflux in isolated adult rat ventricular cardiomyocytes. Am. J. Physiol., 1992, 262, H1699-H1704
34. Elrod, J.W.; Wong, R.; Mishra, S.; Vagnozzi, R.J.; Sakthievel, B.; Goonasekera, S.A.; Karch, J.; Gabel, S.; Farber, J.; Force, T.; Brown, J.H.; Murphy, E.; Molkentin, J.D. Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J. Clin. Invest, 2010, 120, 3680-3687
35. Marzo, I.; Brenner, C.; Zamzami, N.; Susin, S.A.; Beutner, G.; Brdiczka, D.; Remy, R.; Xie, Z.H.; Reed, J.C.; Kroemer, G. The permeability transition pore complex: a target for apoptosis regulation by caspases and bcl-2-related proteins. J. Exp. Med., 1998, 187, 1261-1271
36. Elrod, J.W.; Molkentin, J.D. Physiologic functions of cyclophilin D and the mitochondrial permeability transition pore. Circ. J., 2013, 77, 1111-1122
37. Giorgio, V.; von Stockum, S.; Antoniel, M.; Fabbro, A.; Fogolari, F.; Forte, M.; Glick, G.D.; Petronilli, V.; Zoratti, M.; Szabo, I.; Lippe, G.; Bernardi, P. Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc. Natl. Acad. Sci. U.S.A., 2013, 110, 5887-5892
38. Bonora, M.; Bononi, A.; De Marchi, E.; Giorgi, C.; Lebiedzinska, M.; Marchi, S.; Patergnani, S.; Rimessi, A.; Suski, J.M.; Wojtala, A.; Wieckowski, M.R.; Kroemer, G.; Galluzzi, L.; Pinton, P. Role of the c subunit of the FO ATP synthase in mitochondrial permeability transition. Cell Cycle, 2013, 12, 674-683
39. Alavian, K.N.; Beutner, G.; Lazrove, E.; Sacchetti, S.; Park, H.A.; Licznerski, P.; Li, H.; Nabili, P.; Hockensmith, K.; Graham, M.; Porter, G.A., Jr.; Jonas, E.A. An uncoupling channel within the csubunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proc. Natl. Acad. Sci. U.S.A., 2014, 111, 10580-10585
40. Bernardi, P.; Di Lisa, F. The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. J. Mol. Cell. Cardiol., 2015, 78C, 100-106
41. Ichas, F.; Jouaville, L.S.; Sidash, S.S.; Mazat, J.P.; Holmuhamedov, E.L. Mitochondrial calcium spiking: a transduction mechanism based on calcium-induced permeability transition involved in cell calcium signalling. FEBS Lett., 1994, 348, 211-215
42. Fontaine, E.; Ichas, F.; Bernardi, P. A ubiquinone-binding site regulates the mitochondrial permeability transition pore. J. Biol. Chem., 1998, 273, 25734-25740
43. Petronilli, V.; Miotto, G.; Canton, M.; Brini, M.; Colonna, R.; Bernardi, P.; Di Lisa, F. Transient and long-lasting openings of the mitochondrial permeability transition pore can be monitored directly in intact cells by changes in mitochondrial calcein fluorescence. Biophys. J., 1999, 76, 725-734
44. Bernardi, P.; Scorrano, L.; Colonna, R.; Petronilli, V.; Di Lisa, F. Mitochondria and cell death. Mechanistic aspects and methodological issues. Eur. J. Biochem., 1999, 264, 687-701
45. Petronilli, V.; Penzo, D.; Scorrano, L.; Bernardi, P.; Di Lisa, F. The mitochondrial permeability transition, release of cytochrome c and cell death. Correlation with the duration of pore openings in situ. J. Biol. Chem., 2001, 276, 12030-12034
46. Griffiths, E.J.; Halestrap, A.P. Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem. J., 1995, 307, 93-98
47. Di Lisa, F.; Menabò, R.; Canton, M.; Barile, M.; Bernardi, P. Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in post-ischemic reperfusion of the heart. J. Biol. Chem., 2001, 276, 2571-2575
48. Halestrap, A.P.; Clarke, S.J.; Javadov, S.A. Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc. Res., 2004, 61, 372-385
49. Zorov, D.B.; Juhaszova, M.; Yaniv, Y.; Nuss, H.B.; Wang, S.; Sollott, S.J. Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovasc. Res., 2009, 83, 213-225
50. Juhaszova, M.; Zorov, D.B.; Kim, S.H.; Pepe, S.; Fu, Q.; Fishbein, K.W.; Ziman, B.D.; Wang, S.; Ytrehus, K.; Antos, C.L.; Olson, E.N.; Sollott, S.J. Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J. Clin. Invest, 2004, 113, 1535-1549
51. Wang, S.B.; Murray, C.I.; Chung, H.S.; Van Eyk, J.E. Redox regulation of mitochondrial ATP synthase. Trends Cardiovasc. Med, 2013, 23, 14-18
52. Nguyen, T.T.; Stevens, M.V.; Kohr, M.; Steenbergen, C.; Sack, M.N.; Murphy, E. Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore. J. Biol. Chem., 2011, 286, 40184-40192
53. Chouchani, E.T.; Methner, C.; Nadtochiy, S.M.; Logan, A.; Pell, V.R.; Ding, S.; James, A.M.; Cocheme, H.M.; Reinhold, J.; Lilley, K.S.; Partridge, L.; Fearnley, I.M.; Robinson, A.J.; Hartley, R.C.; Smith, R.A.; Krieg, T.; Brookes, P.S.; Murphy, M.P. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat. Med., 2013, 19, 753-759
54. Taylor, S.W.; Fahy, E.; Murray, J.; Capaldi, R.A.; Ghosh, S.S. Oxidative post-translational modification of tryptophan residues in cardiac mitochondrial proteins. J. Biol. Chem., 2003, 278, 19587-19590
55. Petronilli, V.; Sileikyte, J.; Zulian, A.; Dabbeni-Sala, F.; Jori, G.; Gobbo, S.; Tognon, G.; Nikolov, P.; Bernardi, P.; Ricchelli, F. Switch from inhibition to activation of the mitochondrial permeability transition during hematoporphyrin-mediated photooxidative stress. Unmasking pore-regulating external thiols. Biochim. Biophys. Acta, 2009, 1787, 897-904
56. Sileikyte, J.; Blachly-Dyson, E.; Sewell, R.; Carpi, A.; Menabo, R.; Di Lisa, F.; Ricchelli, F.; Bernardi, P.; Forte, M. Regulation of the Mitochondrial Permeability Transition Pore by the Outer Membrane does not Involve the Peripheral Benzodiazepine Receptor (TSPO). J. Biol. Chem., 2014, 289, 13769-81
57. O'Shea, K.M.; Khairallah, R.J.; Sparagna, G.C.; Xu, W.; Hecker, P.A.; Robillard-Frayne, I.; Des, R.C.; Kristian, T.; Murphy, R.C.; Fiskum, G.; Stanley, W.C. Dietary omega-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca2+-induced permeability transition. J. Mol. Cell. Cardiol., 2009, 47, 819-827
58. Acehan, D.; Malhotra, A.; Xu, Y.; Ren, M.; Stokes, D.L.; Schlame, M. Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria. Biophys. J., 2011, 100, 2184-2192
59. Wang, P.; Heitman, J. The cyclophilins. Genome Biol., 2005, 6, 226
60. Handschumacher, R.E.; Harding, M.W.; Rice, J.; Drugge, R.J.; Speicher, D.W. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science, 1984, 226, 544-547
61. Takahashi, N.; Hayano, T.; Suzuki, M. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature, 1989, 337, 473-475
62. Liu, J.; Farmer, J.D., Jr.; Lane, W.S.; Friedman, J.; Weissman, I.; Schreiber, S.L. Calcineurin is a common target of cyclophilincyclosporin A and FKBP-FK506 complexes. Cell, 1991, 66, 807-815
63. Griffith, J.P.; Kim, J.L.; Kim, E.E.; Sintchak, M.D.; Thomson, J.A.; Fitzgibbon, M.J.; Fleming, M.A.; Caron, P.R.; Hsiao, K.; Navia, M.A. X-ray structure of calcineurin inhibited by the immunophilinimmunosuppressant FKBP12-FK506 complex. Cell, 1995, 82, 507-522
64. Clipstone, N.A.; Crabtree, G.R. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature, 1992, 357, 695-697
65. Walsh, C.T.; Zydowsky, L.D.; McKeon, F.D. Cyclosporin A, the cyclophilin class of peptidylprolyl isomerases, and blockade of T cell signal transduction. J. Biol. Chem., 1992, 267, 13115-13118
66. Macian, F. NFAT proteins: key regulators of T-cell development and function. Nature reviews. Immunology, 2005, 5, 472-484
67. Bennett, W.M.; Norman, D.J. Action and toxicity of cyclosporine. Annu. Rev. Med., 1986, 37, 215-224
68. Nguyen, N.S.; Cottet-Maire, F.; Buetler, T.M.; Lo Russo, A.; Krauskopf, A.S.; Armstrong, J.M.; Vickers, A.E.; Mace, K.; Ruegg, U.T. Metabolism-dependent stimulation of reactive oxygen species and DNA synthesis by cyclosporin A in rat smooth muscle cells. Free Radic. Biol. Med., 1999, 27, 1267-1275
69. Krauskopf, A.; Buetler, T.M.; Nguyen, N.S.; Mace, K.; Ruegg, U.T. Cyclosporin A-induced free radical generation is not mediated by cytochrome P-450. Br. J. Pharmacol., 2002, 135, 977-986
70. Krauskopf, A.; Lhote, P.; Mutter, M.; Dufour, J.F.; Ruegg, U.T.; Buetler, T.M. Vasopressin type 1A receptor up-regulation by cyclosporin A in vascular smooth muscle cells is mediated by superoxide. J. Biol. Chem., 2003, 278, 41685-41690
71. Mihatsch, M.J.; Olivieri, W.; Marbet, U.; Thiel, G.; Harder, F.; Zollinger, H.U. Giant mitochondria in renal tubular cells and cyclosporin A. Lancet, 1981, 1, 1162-1163
72. Fournier, N.; Ducet, G.; Crevat, A. Action of cyclosporine on mitochondrial calcium fluxes. J. Bioenerg. Biomembr., 1987, 19, 297-303
73. Jung, K.; Pergande, M. Influence of cyclosporin A on the respiration of isolated rat kidney mitochondria. FEBS Lett., 1985, 183, 167-169
74. Crompton, M.; Ellinger, H.; Costi, A. Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem. J., 1988, 255, 357-360
75. Broekemeier, K.M.; Dempsey, M.E.; Pfeiffer, D.R. Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J. Biol. Chem., 1989, 264, 7826-7830
76. Halestrap, A.P.; Davidson, A.M. Inhibition of Ca2(+)-induced largeamplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase. Biochem. J., 1990, 268, 153-160
77. Tanveer, A.; Virji, S.; Andreeva, L.; Totty, N.F.; Hsuan, J.J.; Ward, J.M.; Crompton, M. Involvement of cyclophilin D in the activation of a mitochondrial pore by Ca2+ and oxidant stress. Eur. J. Biochem. FEBS, 1996, 238, 166-172
78. Baines, C.P.; Kaiser, R.A.; Purcell, N.H.; Blair, N.S.; Osinska, H.; Hambleton, M.A.; Brunskill, E.W.; Sayen, M.R.; Gottlieb, R.A.; Dorn, G.W.; Robbins, J.; Molkentin, J.D. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature, 2005, 434, 658-662
79. Basso, E.; Fante, L.; Fowlkes, J.; Petronilli, V.; Forte, M.A.; Bernardi, P. Properties of the permeability transition pore in mitochondria devoid of Cyclophilin D. J. Biol. Chem., 2005, 280, 18558-18561
80. Nakagawa, T.; Shimizu, S.; Watanabe, T.; Yamaguchi, O.; Otsu, K.; Yamagata, H.; Inohara, H.; Kubo, T.; Tsujimoto, Y. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature, 2005, 434, 652-658
81. Schinzel, A.C.; Takeuchi, O.; Huang, Z.; Fisher, J.K.; Zhou, Z.; Rubens, J.; Hetz, C.; Danial, N.N.; Moskowitz, M.A.; Korsmeyer, S.J. Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia. Proc. Natl. Acad. Sci .U.S.A, 2005, 102, 12005-12010
82. Hausenloy, D.J.; Boston-Griffiths, E.A.; Yellon, D.M. Cyclosporin A and cardioprotection: from investigative tool to therapeutic agent. Br. J. Pharmacol., 2012, 165, 1235-1245
83. Morel, O.; Perret, T.; Delarche, N.; Labeque, J.N.; Jouve, B.; Elbaz, M.; Piot, C.; Ovize, M. Pharmacological approaches to reperfusion therapy. Cardiovasc. Res., 2012, 94, 246-252
84. Dow, J.; Kloner, R.A. Postconditioning does not reduce myocardial infarct size in an in vivo regional ischemia rodent model. J. Cardiovasc. Pharmacol. Ther., 2007, 12, 153-163
85. Karlsson, L.O.; Zhou, A.X.; Larsson, E.; Astrom-Olsson, K.; Mansson, C.; Akyurek, L.M.; Grip, L. Cyclosporine does not reduce myocardial infarct size in a porcine ischemia-reperfusion model. J. Cardiovasc. Pharmacol. Ther., 2010, 15, 182-189
86. Ruiz-Meana, M.; Inserte, J.; Fernandez-Sanz, C.; Hernando, V.; Miro-Casas, E.; Barba, I.; Garcia-Dorado, D. The role of mitochondrial permeability transition in reperfusion-induced cardiomyocyte death depends on the duration of ischemia. Basic Res. Cardiol., 2011, 106, 1259-1268
87. Pain, T.; Yang, X.M.; Critz, S.D.; Yue, Y.; Nakano, A.; Liu, G.S.; Heusch, G.; Cohen, M.V.; Downey, J.M. Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ. Res., 2000, 87, 460-466
88. Griffiths, E.J.; Halestrap, A.P. Protection by Cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. J. Mol. Cell. Cardiol., 1993, 25, 1461-1469
89. Menazza, S.; Wong, R.; Nguyen, T.; Wang, G.; Gucek, M.; Murphy, E. CypD(-/-) hearts have altered levels of proteins involved in Krebs cycle, branch chain amino acid degradation and pyruvate metabolism. J. Mol. Cell. Cardiol., 2013, 56, 81-90
90. Luvisetto, S.; Basso, E.; Petronilli, V.; Bernardi, P.; Forte, M. Enhancement of anxiety, facilitation of avoidance behavior, and occurrence of adult-onset obesity in mice lacking mitochondrial cyclophilin D. Neuroscience, 2008, 155, 585-596
91. Li, B.; Chauvin, C.; De Paulis, D.; De Oliveira, F.; Gharib, A.; Vial, G.; Lablanche, S.; Leverve, X.; Bernardi, P.; Ovize, M.; Fontaine, E. Inhibition of complex I regulates the mitochondrial permeability transition through a phosphate-sensitive inhibitory site masked by cyclophilin D. Biochim. Biophys. Acta, 2012, 1817, 1628-1634
92. Matas, J.; Young, N.T.; Bourcier-Lucas, C.; Ascah, A.; Marcil, M.; Deschepper, C.F.; Burelle, Y. Increased expression and intramitochondrial translocation of cyclophilin-D associates with increased vulnerability of the permeability transition pore to stress-induced opening during compensated ventricular hypertrophy. J. Mol. Cell. Cardiol., 2009, 46, 420-430
93. Nguyen, T.T.; Wong, R.; Menazza, S.; Sun, J.; Chen, Y.; Wang, G.; Gucek, M.; Steenbergen, C.; Sack, M.N.; Murphy, E. Cyclophilin D modulates mitochondrial acetylome. Circ. Res., 2013, 113, 1308-1319
94. Giorgio, V.; Bisetto, E.; Soriano, M.E.; Dabbeni-Sala, F.; Basso, E.; Petronilli, V.; Forte, M.A.; Bernardi, P.; Lippe, G. Cyclophilin D Modulates Mitochondrial F0F1-ATP Synthase by Interacting with the Lateral Stalk of the Complex. J. Biol. Chem., 2009, 284, 33982-33988
95. Hausenloy, D.J.; Lim, S.Y.; Ong, S.G.; Davidson, S.M.; Yellon, D.M. Mitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning. Cardiovasc. Res, 2010, 88(1), 67-74
96. Belaidi, E.; Decorps, J.; Augeul, L.; Durand, A.; Ovize, M. Endoplasmic reticulum stress contributes to heart protection induced by cyclophilin D inhibition. Basic Res. Cardiol., 2013, 108, 363
97. Cereghetti, G.M.; Stangherlin, A.; Martins de, B.O.; Chang, C.R.; Blackstone, C.; Bernardi, P.; Scorrano, L. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl. Acad. Sci. U.S.A, 2008, 105, 15803-15808
98. Zenke, G.; Strittmatter, U.; Fuchs, S.; Quesniaux, V.F.; Brinkmann, V.; Schuler, W.; Zurini, M.; Enz, A.; Billich, A.; Sanglier, J.J.; Fehr, T. Sanglifehrin A, a novel cyclophilin-binding compound showing immunosuppressive activity with a new mechanism of action. J. Immunol., 2001, 166, 7165-7171
99. Noser, J.A.; Towers, G.J.; Sakuma, R.; Dumont, J.M.; Collins, M.K.; Ikeda, Y. Cyclosporine increases human immunodeficiency virus type 1 vector transduction of primary mouse cells. J. Virol., 2006, 80, 7769-7774
100. Rosenwirth, B.; Billich, A.; Datema, R.; Donatsch, P.; Hammerschmid, F.; Harrison, R.; Hiestand, P.; Jaksche, H.; Mayer, P.; Peichl, P. Inhibition of human immunodeficiency virus type 1 replication by SDZ NIM 811, a nonimmunosuppressive cyclosporine analog. Antimicrob. Agents Chemother., 1994, 38, 1763-1772
101. Clarke, S.J.; McStay, G.P.; Halestrap, A.P. Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A. J. Biol. Chem., 2002, 277, 34793-34799
102. Argaud, L.; Gateau-Roesch, O.; Muntean, D.; Chalabreysse, L.; Loufouat, J.; Robert, D.; Ovize, M. Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. J. Mol. Cell. Cardiol., 2005, 38, 367-374
103. Gomez, L.; Thibault, H.; Gharib, A.; Dumont, J.M.; Vuagniaux, G.; Scalfaro, P.; Derumeaux, G.; Ovize, M. Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice. Am. J. Physiol. Heart Circ. Physiol., 2007, 293, H1654-H1661
104. D'Angelo, G.; Duplan, E.; Vigne, P.; Frelin, C. Cyclosporin A prevents the hypoxic adaptation by activating hypoxia-inducible factor-1alpha Pro-564 hydroxylation. J. Biol. Chem., 2003, 278, 15406-15411
105. Bordet, T.; Buisson, B.; Michaud, M.; Drouot, C.; Galea, P.; Delaage, P.; Akentieva, N.P.; Evers, A.S.; Covey, D.F.; Ostuni, M.A.; Lacapere, J.J.; Massaad, C.; Schumacher, M.; Steidl, E.M.; Maux, D.; Delaage, M.; Henderson, C.E.; Pruss, R.M. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J. Pharmacol. Exp. Ther., 2007, 322, 709-720
106. Schaller, S.; Paradis, S.; Ngoh, G.A.; Assaly, R.; Buisson, B.; Drouot, C.; Ostuni, M.A.; Lacapere, J.J.; Bassissi, F.; Bordet, T.; Berdeaux, A.; Jones, S.P.; Morin, D.; Pruss, R.M. TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition. J. Pharmacol. Exp. Ther., 2010, 333, 696-706
107. Atar, D.; Arheden, H.; Berdeaux, A.; Bonnet, J.L.; Carlsson, M.; Clemmensen, P.; Cuvier, V.; Danchin, N.; Dubois-Rande, J.L.; Engblom, H.; Erlinge, D.; Firat, H.; Halvorsen, S.; Hansen, H.S.; Hauke, W.; Heiberg, E.; Koul, S.; Larsen, A.I.; Le Corvoisier, P.; Nordrehaug, J.E.; Paganelli, F.; Pruss, R.M.; Rousseau, H.; Schaller, S.; Sonou, G.; Tuseth, V.; Veys, J.; Vicaut, E.; Jensen, S.E. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur. Heart J., 2014, 36(2), 112-9
108. Fancelli, D.; Abate, A.; Amici, R.; Bernardi, P.; Ballarini, M.; Cappa, A.; Carenzi, G.; Colombo, A.; Contursi, C.; Di Lisa, F.; Dondio, G.; Gagliardi, S.; Milanesi, E.; Minucci, S.; Pain, G.; Pelicci, P.G.; Saccani, A.; Storto, M.; Thaler, F.; Varasi, M.; Villa, M.; Plyte, S. Cinnamic anilides as new mitochondrial permeability transition pore inhibitors endowed with ischemia-reperfusion injury protective effect in vivo. J. Med. Chem.,, 2014, 57, 5333-5347.