Targeting mitochondrial permeability as a pharmacological cardioprotective strategy.
Main Article Content
Abstract
Ischemia-reperfusion injury is a leading cause of death in Western countries. Currently, the only treatment to reduce infact size and to improve the clinical outcome after myocardial ischemia is the rapid restoration of blood flow and the development of reperfusion techniques has strongly reduced the morbidity and mortality in patients. However, the efficacy of this clinical approach is limited because cardiac reperfusion per se give birth to cellular injury. During the last decades, multiple studies demonstrated that the pathological signals induced by ischemia-reperfusion converge towards mitochondria and that most of cell death in the heart is induced by the permeabilization of mitochondrial membranes in the early reperfusion. The search for drugs able to block or to inhibit mitochondrial membrane permeabilization has been the subject of growing interest. It gave birth to several pharmacological approaches to protect from myocardial ischemia-reperfusion injury in experimental models and clinical settings. This review describes these mitochondrial-targeting strategies with a focus on new pharmacological approaches which constitute real hope for the future.
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References
2. Gustafsson AB, Gottlieb RA. Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol. 2007;292(1):C45-C51.
3. Morciano G, Giorgi C, Bonora M, Punzetti S, Pavasini R, Wieckowski MR, Campo G, Pinton P. Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury. J Mol Cell Cardiol. 2015 Jan;78:142-53.
4. Szabo, I., Zoratti, M. Mitochondrial channels: ion fluxes and more. Physiol Rev. 2014;94(2):519-608.
5. Halestrap AP, Richardson AP. The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia/reperfusion injury. J Mol Cell Cardiol. 2015 Jan;78:129-41.
6. Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999;341(Pt 2):233-49.
7. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007;357(11):1121-35.
8. Morin D, Assaly R, Paradis S, Berdeaux A. Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection. Curr Med Chem. 2009;16(33):4382-98
9. Halestrap AP.A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection. Biochem Soc Trans. 2010 Aug;38(4):841-60
10. Di Lisa F, Canton M, Carpi A, Kaludercic N, Menabò R, Menazza S, Semenzato M. Mitochondrial injury and protection in ischemic pre- and postconditioning. Antioxid Redox Signal. 2011;14(5):881-91.
11. Murry, C.E.; Jennings, R.B.; Reimer, K.A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74(5):1124-1136.
12. Hausenloy DJ, Tsang A, Mocanu MM, Yellon DM. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol. 2005a;288(2):H971-6.
13. Auchampach JA, Grover GJ, Gross GJ. Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate. Cardiovasc Res. 1992;26(11):1054-62.
14. Liu Y, Ytrehus K, Downey JM. Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. J Mol Cell Cardiol. 1994;26(5):661-8
15. Lecour S. Activation of the protective Survivor Activating Factor Enhancement (SAFE) pathway against reperfusion injury: Does it go beyond the RISK pathway? J Mol Cell Cardiol. 2009;47(1):32-40.
16. Skyschally A, van Caster P, Boengler K, Gres P, Musiolik J, Schilawa D, Schulz R, Heusch G. Ischemic postconditioning in pigs: no causal role for RISK activation. Circ Res. 2009;104(1):15-8.
17. Davidson SM, Hausenloy D, Duchen MR, Yellon DM. Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection. Int J Biochem Cell Biol. 2006;38(3):414-9.
18. Boengler K, Hilfiker-Kleiner D, Heusch G, Schulz R. Inhibition of permeability transition pore opening by mitochondrial STAT3 and its role in myocardial ischemia/reperfusion. Basic Res Cardiol. 2010;105(6):771-85.
19. Hausenloy DJ, Tsang A, Yellon DM. The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med. 2005b;15:69-75.
20. Li J, Xuan W, Yan R, Tropak MB, Jean-St-Michel E, Liang W, Gladstone R, Backx PH, Kharbanda RK, Redington AN Remote preconditioning provides potent cardioprotection via PI3K/Akt activation and is associated with nuclear accumulation of β-catenin. Clin Sci (Lond). 2011;120(10):451-62.
21. Turrell HE, Thaitirarot C, Crumbie H, Rodrigo G. Remote ischemic preconditioning of cardiomyocytes inhibits the mitochondrial permeability transition pore independently of reduced calcium-loading or sarcKATP channel activation. Physiol Rep. 2014;2(11). pii: e12231.
22. Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G. Across-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways. Circ Res. 2015;117(3):279-88.
23. Liu GS, Thornton J, Van Winkle DM, Stanley AW, Olsson RA, Downey JM. Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation. 1991;84(1):350-6.
24. Marzilli M.; Orsini E.; Marraccini P.; Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation, 2000, 101(18), 2154-2159.
25. Quintana M.; Hjemdahl P.; Sollevi A.; Kahan T.; Edner M.; Rehnqvist N.; Swahn E.; Kjerr A.C.; Näsman P.; ATTACC investigators. Left ventricular function and cardiovascular events following adjuvant therapy with adenosine in acute myocardial infarction treated with thrombolysis, results of the ATTenuation by Adenosine of Cardiac Complications (ATTACC) study. Eur. J. Clin. Pharmacol., 2003, 59(1), 1-9.
26. Mahaffey K.W.; Puma J.A.; Barbagelata N.A.; DiCarli M.F.; Leesar M.A.; Browne K.F.; Eisenberg P.R.; Bolli R.; Casas A.C.; Molina-Viamonte V.; Orlandi C.; Blevins R.; Gibbons R.J.; Califf R.M.; Granger C.B. Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial. J. Am. Coll. Cardiol., 1999, 34(6), 1711-1720.
27. Ross A.M.; Gibbons R.J.; Stone G.W.; Kloner R.A.; Alexander R.W. AMISTAD-II Investigators. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J. Am. Coll. Cardiol., 2005, 45(11), 1775-1780.
28. Polimeni A, De Rosa S, Sabatino J, Sorrentino S, Indolfi C. Impact of intracoronary adenosine administration during primary PCI: A meta-analysis. Int J Cardiol. 2016 Jan 15;203:1032-41
29. Gross, E.R.; Hsu, A.K.; Gross, G.J. Opioid-induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ. Res., 2004, 94(7), 960-966.
30. Obame, F.N.; Plin-Mercier, C.; Assaly, R.; Zini, R.; Dubois-Randé, J.L.; Berdeaux, A.; Morin, D. Cardioprotective effect of morphine and a blocker of glycogen synthase kinase 3 beta, SB216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via inhibition of the mitochondrial permeability transition pore. J Pharmacol Exp Ther., 2008, 326(1), 252-258.
31. Rentoukas I, Giannopoulos G, Kaoukis A, Kossyvakis C, Raisakis K, Driva M, Panagopoulou V, Tsarouchas K, Vavetsi S, Pyrgakis V, Deftereos S. Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc Interv. 2010;3(1):49-55.
32. Zhang R, Shen L, Xie Y, Gen L, Li X, Ji Q. Effect of morphine-induced postconditioning in corrections of tetralogy of fallot. J Cardiothorac Surg. 2013 Apr 11;8:76
33. Gwag HB, Kim EK1, Park TK, Lee JM, Yang JH, Song YB, Choi JH, Choi SH, Lee SH, Chang SA, Park SJ, Lee SC, Park SW, Jang WJ, Lee M, Chun WJ, Oh JH, Park YH, Choe YH, Gwon HC, Hahn JY. Cardioprotective Effects of Intracoronary Morphine in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: A Prospective, Randomized Trial. J Am Heart Assoc. 2017;6(4). pii: e005426.
34. Schulman D, Latchman DS, Yellon DM Urocortin protects the heart from reperfusion injury via upregulation of p42/p44 MAPK signaling pathway. Am J Physiol Heart Circ Physiol. 2002, 283(4):H1481–H1488
35. Bose AK, Mocanu MM, Carr RD, Yellon DM Glucagon like peptide-1 is protective against myocardial ischemia/reperfusion injury when given either as a preconditioning mimetic or at reperfusion in an isolated rat heart model. Cardiovasc Drugs Ther. 2005 19(1):9–11
36. Hausenloy DJ, Yellon DM Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection. Heart Fail Rev. 2007;12:217-34.
37. Guillard C, Chretien S, Pelus AS, Porteu F, Muller O, Mayeux P, Duprez V. Activation of the mitogen-activated protein kinases Erk1/2 by erythropoietin receptor via a G(i)protein beta gamma-subunit-initiated pathway. J Biol Chem 2003, 278:11050–11056
38. Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 2003, 100(8):4802–4806
39. Tramontano AF, Muniyappa R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV, El-Sherif N. Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun 2003, 308(4):990–994
40. Hanlon PR, Fu P, Wright GL, Steenbergen C, Arcasoy MO, Murphy E Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase signaling. FASEB J 2005, 19(10):1323–1325
41. Ott I, Schulz S, Mehilli J, Fichtner S, Hadamitzky M, Hoppe K, Ibrahim T, Martinoff S, Massberg S, Laugwitz KL, Dirschinger J, Schwaiger M, Kastrati A, Schmig A; REVIVAL-3 Study Investigators. Erythropoietin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized, double-blind trial. Circ Cardiovasc Interv. 2010 ; 3(5):408-13
42. Najjar SS, Rao SV, Melloni C, Raman SV, Povsic TJ, Melton L, Barsness GW, Prather K, Heitner JF, Kilaru R, Gruberg L, Hasselblad V, Greenbaum AB, Patel M, Kim RJ, Talan M, Ferrucci L, Longo DL, Lakatta EG, Harrington RA; REVEAL Investigators. JAMA. 2011 ;305(18):1863-72.
43. Ludman AJ, Yellon DM, Hasleton J, Ariti C, Babu GG, Boston-Griffiths E, Venugopal V, Walker M, Holdright D, Swanton H, Crake T, Brull D, Moon JC, Puranik R, Muthurangu V, Taylor A, Hausenloy DJ. Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial. Heart. 2011 ;97(19):1560-5.
44. Prunier F, Bière L, Gilard M, Boschat J, Mouquet F, Bauchart JJ, Charbonnier B, Genée O, Guérin P, Warin-Fresse K, Durand E, Lafont A, Christiaens L, Abi-Khalil W, Delépine S, Benard T, Furber A. Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial. Am Heart J. 2012 ;163(2):200-7.
45. Taniguchi N, Nakamura T, Sawada T, Matsubara K, Furukawa K, Hadase M, Nakahara Y, Nakamura T, Matsubara H. Erythropoietin prevention trial of coronary restenosis and cardiac remodeling after ST-elevated acute myocardial infarction (EPOC-AMI): a pilot, randomized, placebo-controlled study. Circ J. 2010 ;74(11):2365-71.
46. Minamino T, Toba K, Higo S, Nakatani D, Hikoso S, Umegaki M, Yamamoto K, Sawa Y, Aizawa Y, Komuro I; EPO-AMI-II study investigators. Design and rationale of low-dose erythropoietin in patients with ST-segment elevation myocardial infarction (EPO-AMI-II study): a randomized controlled clinical trial. Cardiovasc Drugs Ther. 2012;26(5):409-16.
47. Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, Sessa WC, Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6(9):1004-10.
48. Sanada S, Asanuma H, Minamino T, Node K, Takashima S, Okuda H, Shinozaki Y, Ogai A, Fujita M, Hirata A, Kim J, Asano Y, Mori H, Tomoike H, Kitamura S, Hori M, Kitakaze M. Optimal windows of statin use for immediate infarct limitation: 5’-nucleotidase as another downstream molecule of phosphatidylinositol 3-kinase. Circulation 2004;110(15):2143–2149.
49. Efthymiou CA, Mocanu MM, Yellon DM Atorvastatin and myocardial reperfusion injury: new pleiotropic effect implicating multiple prosurvival signaling. J Cardiovasc Pharmacol. 2005; 45(3):247-52.
50. Jones, S.P.; Teshima, Y.; Akao, M.; Marbán, E. Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res. 2003;93(8):697-699.
51. Pan Y, Tan Y, Li B, Li X Efficacy of high-dose rosuvastatin preloading in patients undergoing percutaneous coronary intervention: a meta-analysis of fourteen randomized controlled trials. Lipids Health Dis. 2015 Aug 27;14:97.
52. Benjo AM, El-Hayek GE, Messerli F, DiNicolantonio JJ, Hong MK, Aziz EF, Herzog E, Tamis-Holland JE.High dose statin loading prior to percutaneous coronary intervention decreases cardiovascular events: a meta-analysis of randomized controlled trials. Catheter Cardiovasc Interv. 2015; 85(1):53-60.
53. Bates E, Bode C, Costa M, Gibson CM, Granger C, Green C, Grimes K, Harrington R, Huber K, Kleiman N, Mochly-Rosen D, Roe M, Sadowski Z, Solomon S, Widimsky P. Intracoronary KAI-9803 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction. Circulation. 2008; 117(7):886-96
54. Lincoff AM, Roe M, Aylward P, Galla J, Rynkiewicz A, Guetta V, Zelizko M, Kleiman N, White H, McErlean E, Erlinge D, Laine M, Dos Santos Ferreira JM, Goodman S, Mehta S, Atar D, Suryapranata H, Jensen SE, Forster T, Fernandez-Ortiz A, Schoors D, Radke P, Belli G, Brennan D, Bell G, Krucoff M; PROTECTION AMI Investigators. Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial. Eur Heart J. 2014; 35(37):2516-23
55. Lamont KT, Somers S, Lacerda L, Opie LH, Lecour S. Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection. J Pineal Res. 2011;50(4):374-80
56. Frias MA, Lecour S, James RW, Pedretti S. High density lipoprotein/sphingosine-1-phosphate-induced cardioprotection: Role of STAT3 as part of the SAFE pathway. JAKSTAT. 2012;1(2):92-100.
57. Lochner A, Huisamen B, Nduhirabandi F. Cardioprotective effect of melatonin against ischaemia/reperfusion damage. Front Biosci. 2013 Jan 1;5:305-15.
58. Kwan JC, Gao L, Macdonald PS, Hicks M. Cardio-protective signalling by glyceryl trinitrate and cariporide in a model of donor heart preservation. Heart Lung Circ. 2015;24(3):306-18.
59. Somers SJ, Frias M, Lacerda L, Opie LH, Lecour S. Interplay between SAFE and RISK pathways in sphingosine-1-phosphate-induced cardioprotection. Cardiovasc Drugs Ther. 2012;26(3):227-37.
60. Dorsch M, Behmenburg F, Raible M, Blase D, Grievink H, Hollmann MW, Heinen A, Huhn R. Morphine-Induced Preconditioning: Involvement of Protein Kinase A and Mitochondrial Permeability Transition Pore. PLoS One. 2016;11(3):e0151025.
61. Brulhart-Meynet MC, Braunersreuther V, Brinck J, Montecucco F, Prost JC, Thomas A, Galan K, Pelli G, Pedretti S, Vuilleumier N, Mach F, Lecour S, James RW, Frias MA. Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury. PLoS One. 2015; 10(3):e0119664.
62. Watson AJ, Gao L, Sun L, Tsun J, Jabbour A, Ru Qiu M, Jansz PC, Hicks M, Macdonald PS. Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution. J Heart Lung Transplant. 2013; 32(6):633-40.
63. Lemoine S, Zhu L, Legallois D, Massetti M, Manrique A, Hanouz JL. Atorvastatin-induced cardioprotection of human myocardium is mediated by the inhibition of mitochondrial permeability transition pore opening via tumor necrosis factor-α and Janus kinase/signal transducers and activators of transcription pathway. Anesthesiology. 2013; 118(6):1373-84
64. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 2008; 88(2):581-609
65. Wang Y, Meyer JW, Ashraf M, Shull GE Mice with a null mutation in the NHE1 Na+-H+ exchanger are resistant to cardiac ischemia-reperfusion injury. Circ Res. 2003;93(8):776-82.
66. Imahashi K, Pott C, Goldhaber JI, Steenbergen C, Philipson KD, Murphy E. Cardiac-specific ablation of the Na+-Ca2+ exchanger confers protection against ischemia/reperfusion injury. Circ Res. 2005; 97(9):916-21.
67. Avkiran M, Marber MS. Na(+)/H(+) exchange inhibitors for cardioprotective therapy: progress, problems and prospects. J Am Coll Cardiol. 2002; 39(5):747-53.
68. Mentzer RM Jr, Lasley RD, Jessel A, Karmazyn M. Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection. Ann Thorac Surg. 2003; 75(2):S700-8.
69. Namekata I, Shimada H, Kawanishi T, Tanaka H, Shigenobu K. Reduction by SEA0400 of myocardial ischemia-induced cytoplasmic and mitochondrial Ca2+ overload. Eur J Pharmacol. 2006; 543(1-3):108-15.
70. Toda T, Kadono T, Hoshiai M, Eguchi Y, Nakazawa S, Nakazawa H, Higashijima N, Ishida H. Na+/H+ exchanger inhibitor cariporide attenuates the mitochondrial Ca2+ overload and PTP opening. Am J Physiol Heart Circ Physiol. 2007; 293(6):H3517-23.
71. Javadov S, Choi A, Rajapurohitam V, Zeidan A, Basnakian AG, Karmazyn M. NHE-1 inhibition-induced cardioprotection against ischaemia/reperfusion is associated with attenuation of the mitochondrial permeability transition. Cardiovasc Res. 2008;77(2):416-24.
72. Piper HM, Kasseckert S, Abdallah Y The sarcoplasmic reticulum as the primary target of reperfusion protection. Cardiovasc Res. 2006;70(2):170-3.
73. Fauconnier J, Roberge S, Saint N, Lacampagne A Type 2 ryanodine receptor: a novel therapeutic target in myocardial ischemia/reperfusion. Pharmacol Ther. 2013;138(3):323-32.
74. Lopez-Crisosto C, Pennanen C, Vasquez-Trincado C, Morales PE, Bravo-Sagua R, Quest AFG, Chiong M, Lavandero S. Sarcoplasmic reticulum-mitochondria communication in cardiovascular pathophysiology. Nat Rev Cardiol. 2017;14(6):342-360.
75. Shintani-Ishida K, Inui M, Yoshida K. Ischemia-reperfusion induces myocardial infarction through mitochondrial Ca²⁺ overload. J Mol Cell Cardiol. 2012;53(2):233-9
76. Paillard M, Tubbs E, Thiebaut PA, Gomez L, Fauconnier J, Da Silva CC, Teixeira G, Mewton N, Belaidi E, Durand A, Abrial M, Lacampagne A, Rieusset J, Ovize M. Depressing mitochondria-reticulum interactions protects cardiomyocytes from lethal hypoxia-reoxygenation injury. Circulation. 2013;128(14):1555-65.
77. Fazal L, Laudette M, Paula-Gomes S, Pons S, Conte C, Tortosa F, Sicard P, Sainte-Marie Y, Bisserier M, Lairez O, Lucas A, Roy J, Ghaleh B, Fauconnier J, Mialet-Perez J, Lezoualc'h F. Multifunctional Mitochondrial Epac1 Controls Myocardial Cell Death. Circ Res. 2017;120(4):645-657.
78. Harrington JL, Murphy E The mitochondrial calcium uniporter: mice can live and die without it. J Mol Cell Cardiol. 2015 Jan;78:46-53.
79. Miyamae M, Camacho SA, Weiner MW, Figueredo VM. Attenuation of postischemic reperfusion injury is related to prevention of [Ca2+]m overload in rat hearts. Am J Physiol. 1996;271(5 Pt 2):H2145-53
80. de Jesús García-Rivas G, Guerrero-Hernández A, Guerrero-Serna G, Rodríguez-Zavala JS, Zazueta C Inhibition of the mitochondrial calcium uniporter by the oxo-bridged dinuclear ruthenium amine complex (Ru360) prevents from irreversible injury in postischemic rat heart. FEBS J. 2005;272(13):3477-88.
81. García-Rivas G de J, Carvajal K, Correa F, Zazueta C. Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post-ischaemic functional recovery in rats in vivo. Br J Pharmacol. 2006;149(7):829-37
82. Kwong JQ, Lu X, Correll RN, Schwanekamp JA, Vagnozzi RJ, Sargent MA, York AJ, Zhang J, Bers DM, Molkentin JD. The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart. Cell Rep. 2015;12(1):15-22.
83. Rasmussen TP, Wu Y, Joiner ML, Koval OM, Wilson NR, Luczak ED, Wang Q, Chen B, Gao Z, Zhu Z, Wagner BA, Soto J, McCormick ML, Kutschke W, Weiss RM, Yu L, Boudreau RL, Abel ED, Zhan F, Spitz DR, Buettner GR, Song LS, Zingman LV, Anderson ME. Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart. Proc Natl Acad Sci U S A. 2015;112(29):9129-34
84. Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc). 2005;70(2):200-14.
85. Zweier, J.L. Measurement of superoxide-derived free radicals in the reperfused heart. Evidence for a free radical mechanism of reperfusion injury. J Biol Chem, 1988;263(3):1353-1357.
86. Raedschelders K, Ansley DM, Chen DD. The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion. Pharmacol Ther. 2012;133(2):230-55
87. Kim JS, Jin Y, Lemasters JJ. Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2006;290(5):H2024-34
88. Clarke SJ, Khaliulin I, Das M, Parker JE, Heesom KJ, Halestrap AP. Inhibition of mitochondrial permeability transition pore opening by ischemic preconditioning is probably mediated by reduction of oxidative stress rather than mitochondrial protein phosphorylation. Circ Res. 2008;102(9):1082-90
89. Chernyak BV, Bernardi P. The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur J Biochem. 1996;238(3):623-30.
90. Halestrap AP, Woodfield KY, Connern CP. Oxidative stress, thiol reagents, and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase. J Biol Chem. 1997;272(6):3346-54
91. Costantini P, Belzacq AS, Vieira HL, Larochette N, de Pablo MA, Zamzami N, Susin SA, Brenner C, Kroemer G. Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis. Oncogene. 2000;19(2):307-14.
92. Nguyen TT, Stevens MV, Kohr M, Steenbergen C, Sack MN, Murphy E. Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore. J Biol Chem. 2011;286(46):40184-92.
93. Wang SB, Murray CI, Chung HS, Van Eyk JE. Redox regulation of mitochondrial ATP synthase. Trends Cardiovasc Med. 2013;23(1):14-8
94. Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cochemé HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS, Murphy MP. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med. 2013;19(6):753-9.
95. Petrosillo G, Casanova G, Matera M, Ruggiero FM, Paradies G. Interaction of peroxidized cardiolipin with rat-heart mitochondrial membranes: induction of permeability transition and cytochrome c release. FEBS Lett. 2006;580(27):6311-6
96. Seidlmayer LK, Juettner VV, Kettlewell S, Pavlov EV, Blatter LA, Dedkova EN. Distinct mPTP activation mechanisms in ischaemia-reperfusion: contributions of Ca2+, ROS, pH, and inorganic polyphosphate. Cardiovasc Res. 2015;106(2):237-48.
97. DeBoer LW, Bekx PA, Han L, Steinke L Pyruvate enhances recovery of rat hearts after ischemia and reperfusion by preventing free radical generation. Am J Physiol. 1993;265 (5 Pt 2):H1571-6.
98. Kerr PM, Suleiman MS, Halestrap AP. Reversal of permeability transition during recovery of hearts from ischemia and its enhancement by pyruvate. Am J Physiol. 1999;276(2 Pt 2):H496-502
99. Dobsak, P.; Courderot-Masuyer, C.; Zeller, M.; Vergely, C.; Laubriet, A.; Assem, M.; Eicher, J.C.; Teyssier, J.R.; Wolf, J.E.; Rochette, L. Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia. J Cardiovasc. Pharmacol., 1999;34(5):651-59.
100. Oliveira, P.J.; Gonçalves, L.; Monteiro, P.; Providencia, L.A.; Moreno, A..J. Are the antioxidant properties of carvedilol important for the protection of cardiac mitochondria? Curr. Vasc. Pharmacol., 2005;3(2):147-158.
101. Silva FS, Simoes RF, Couto R, Oliveira PJ. Targeting Mitochondria in Cardiovascular Diseases. Curr Pharm Des. 2016;22(37):5698-5717.
102. Javadov SA, Lim KH, Kerr PM, Suleiman MS, Angelini GD, Halestrap AP. Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition. Cardiovasc Res. 2000;45(2):360-9.
103. Kobayashi I, Kokita N, Namiki A. Propofol attenuates ischaemia-reperfusion injury in the rat heart in vivo. Eur J Anaesthesiol. 2008;25(2):144-51.
104. Rajesh, K.G.; Sasaguri, S.; Suzuki, R.; Maeda, H. Antioxidant MCI-186 inhibits mitochondrial permeability transition pore and upregulates Bcl-2 expression. Am. J. Physiol.Heart Circ. Physiol., 2003;285(5):H2171-H2178.
105. Onogi H, Minatoguchi S, Chen XH, Bao N, Kobayashi H, Misao Y, Yasuda S, Yamaki T, Maruyama R, Uno Y, Arai M, Takemura G, Fujiwara H. Edaravone reduces myocardial infarct size and improves cardiac function and remodelling in rabbits. Clin Exp Pharmacol Physiol. 2006;33(11):1035-41
106. Bognar, Z.; Kalai, T.; Palfi, A.; Hanto, K.; Bognar, B.; Mark, L.; Szabo, Z.; Tapodi, A.; Radnai, B.; Sarszegi, Z.; Szanto, A.; Gallyas, F. Jr.; Hideg, K.; Sumegi, B.; Varbiro, G. A novel SOD-mimetic permeability transition inhibitor agent protects ischemic heart by inhibiting both apoptotic and necrotic cell death. Free Radic Biol Med. 2006;41(5):835-848.
107. Petrosillo G, Colantuono G, Moro N, Ruggiero FM, Tiravanti E, Di Venosa N, Fiore T, Paradies G. Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening. Am J Physiol Heart Circ Physiol. 2009;297(4):H1487-93.
108. Griendling, K.K; FitzGerald, G.A. Oxidative stress and cardiovascular injury: Part II: animal and human studies. Circulation. 2003;108(17):2034-2040.
109. Schmidt HH, Stocker R, Vollbracht C, Paulsen G, Riley D, Daiber A, Cuadrado A. Antioxidants in Translational Medicine. Antioxid Redox Signal. 2015;23(14):1130-43
110. Bartekova M, Barancik M, Ferenczyova K, Dhalla NS. Beneficial effects of N-acetylcysteine and N-mercaptopropionylglycine on ischemia reperfusion injury in the heart. Curr Med Chem. 2017 Jun 8. doi: 10.2174/0929867324666170608111917.
111. Pasupathy S, Tavella R, Grover S, Raman B, Procter NEK, Du YT, Mahadavan G, Stafford I, Heresztyn T, Holmes A, Zeitz C, Arstall M, Selvanayagam JB, Horowitz JD, Beltrame JF.Early use of N-Acetylcysteine (NAC) with Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Reduces Myocardial Infarct Size (The NACIAM Trial). Circulation. 2017 Jun 20. doi: 10.1161/CIRCULATIONAHA.117.027575.
112. Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP, Sammut IA. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J. 2005;19(9):1088-95
113. Ziberna L, Lunder M, Moze S, Vanzo A, Tramer F, Passamonti S, Drevensek G. Acute cardioprotective and cardiotoxic effects of bilberry anthocyanins in ischemia-reperfusion injury: beyond concentration-dependent antioxidant activity. Cardiovasc Toxicol. 2010;10(4):283-94.
114. Ajith TA, Jayakumar TG Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases. World J Cardiol. 2014;6(10):1091-9.
115. Jean SR, Ahmed M2, Lei EK3, Wisnovsky SP3, Kelley SO1 Peptide-Mediated Delivery of Chemical Probes and Therapeutics to Mitochondria. Acc Chem Res. 2016;49(9):1893-902.
116. Murphy MP. Targeting lipophilic cations to mitochondria. Biochim Biophys Acta. 2008;1777(7-8):1028-31.
117. Skulachev VP1, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, Filenko OF, Kalinina NI, Kapelko VI, Kolosova NG, Kopnin BP, Korshunova GA, Lichinitser MR, Obukhova LA, Pasyukova EG, Pisarenko OI, Roginsky VA, Ruuge EK, Senin II, Severina II, Skulachev MV, Spivak IM, Tashlitsky VN, Tkachuk VA, Vyssokikh MY, Yaguzhinsky LS, Zorov DB An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta. 2009;1787(5):437-61.
118. Liang HL, Sedlic F, Bosnjak Z, Nilakantan V. SOD1 and MitoTEMPO partially prevent mitochondrial permeability transition pore opening, necrosis, and mitochondrial apoptosis after ATP depletion recovery. Free Radic Biol Med. 2010;49(10):1550-60.
119. Dare AJ, Logan A, Prime TA, Rogatti S, Goddard M, Bolton EM, Bradley JA, Pettigrew GJ, Murphy MP, Saeb-Parsy K. The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model. J Heart Lung Transplant. 2015;34(11):1471-80
120. Horton KL, Stewart KM, Fonseca SB, Guo Q, Kelley SO. Mitochondria-penetrating peptides. Chem Biol. 2008;15(4):375-82.
121. Fink MP, Macias CA, Xiao J, Tyurina YY, Jiang J, Belikova N, Delude RL, Greenberger JS, Kagan VE, Wipf P. Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted anti-oxidants. Biochem Pharmacol. 2007;74(6):801-9.
122. Szeto HH. Development of mitochondria-targeted aromatic-cationic peptides for neurodegenerative diseases. Ann N Y Acad Sci. 2008 Dec;1147:112-21
123. Zhao, K.; Zhao, G.M.; Wu, D.; Soong, Y.; Birk, A.V.; Schiller, P.W.; Szeto, H.H. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J. Biol. Chem. 2004;279(33) :34682-34690.
124. Cho J, Won K, Wu D, Soong Y, Liu S, Szeto HH, Hong MK Potent mitochondria-targeted peptides reduce myocardial infarction in rats. Coron Artery Dis. 2007;18(3):215-20.
125. Birk AV, Chao WM, Bracken C, Warren JD, Szeto HH. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol. 2014;171(8):2017-28
126. Gibson CM, Giugliano RP, Kloner RA, Bode C, Tendera M, Jánosi A, Merkely B, Godlewski J, Halaby R, Korjian S, Daaboul Y, Chakrabarti AK, Spielman K, Neal BJ, Weaver WD. EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J. 2016;37(16):1296-303
127. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR,Wallace DC. The ADP/ATP translocator is not essential for the mitochondrialpermeability transition pore. Nature. 2004;427(6973):461-465.
128. Krauskopf A, Eriksson O, Craigen WJ, Forte MA, Bernardi P. Properties of the permeability transition in VDAC1(-/-) mitochondria. Biochim. Biophys. Acta. 2006;1757(5-6):590-595.
129. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005;434(7033):658-62
130. 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(7033):652-8
131. 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(1):357-60
132. Javadov S, Jang S, Parodi-Rullán R, Khuchua Z, Kuznetsov AV. Mitochondrial permeability transition in cardiac ischemia-reperfusion: whether cyclophilin D is a viable target for cardioprotection? Cell Mol Life Sci. 2017;74(15):2795-2813
133. Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, André-Fouët X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008;359(5):473-81
134. Mewton N, Croisille P, Gahide G, Rioufol G, Bonnefoy E, Sanchez I, Cung TT, Sportouch C, Angoulvant D, Finet G, André-Fouët X, Derumeaux G, Piot C, Vernhet H, Revel D, Ovize M. Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction. J Am Coll Cardiol. 2010;55(12):1200-5
135. Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guérin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Randé JL, Unterseeh T, Le Breton H, Béard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M. Cyclosporine before PCI in Patients with Acute Myocardial Infarction. N Engl J Med. 2015;373(11):1021-31
136. Ottani F, Latini R, Staszewsky L, La Vecchia L, Locuratolo N, Sicuro M, Masson S, Barlera S, Milani V, Lombardi M, Costalunga A, Mollichelli N, Santarelli A, De Cesare N, Sganzerla P, Boi A, Maggioni AP, Limbruno U; CYCLE Investigators. Cyclosporine A in Reperfused Myocardial Infarction: The Multicenter, Controlled, Open-Label CYCLE Trial. J Am Coll Cardiol. 2016;67(4):365-74
137. Chen-Scarabelli C, Scarabelli TM. Cyclosporine A Prior to Primary PCI in STEMI Patients: The Coup de Grâce to Post-Conditioning? J Am Coll Cardiol. 2016;67(4):375-8
138. Heusch G. CIRCUS: a kiss of death for cardioprotection? Cardiovasc Res. 2015;108(2):215-6
139. Monassier L, Ayme-Dietrich E, Aubertin-Kirch G, Pathak A. Targeting myocardial reperfusion injuries with cyclosporine in the CIRCUS Trial – pharmacological reasons for failure. Fundam Clin Pharmacol. 2016;30(2):191-3
140. Malouitre S, Dube H, Selwood D, Crompton M. Mitochondrial targeting of cyclosporin A enables selective inhibition of cyclophilin-D and enhanced cytoprotection after glucose and oxygen deprivation. Biochem J. 2009;425(1):137-48
141. Dube H, Selwood D, Malouitre S, Capano M, Simone MI, Crompton M. A mitochondrial-targeted cyclosporin A with high binding affinity for cyclophilin D yields improved cytoprotection of cardiomyocytes. Biochem J. 2012;441(3):901-7.
142. Warne J, Pryce G, Hill JM, Shi X, Lennerås F, Puentes F, Kip M, Hilditch L, Walker P, Simone MI, Chan AW, Towers GJ, Coker AR, Duchen MR, Szabadkai G, Baker D, Selwood DL. Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis. J Biol Chem. 2016;291(9):4356-73
143. Ikeda G, Matoba T, Nakano Y, Nagaoka K, Ishikita A, Nakano K, Funamoto D, Sunagawa K, Egashira K. Nanoparticle-Mediated Targeting of Cyclosporine A Enhances Cardioprotection Against Ischemia-Reperfusion Injury Through Inhibition of Mitochondrial Permeability Transition Pore Opening. Sci Rep. 2016 Feb 10;6:20467
144. Nicolli A, Basso E, Petronilli V, Wenger RM, Bernardi P. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996;271(4):2185-92
145. Waldmeier PC, Feldtrauer JJ, Qian T, Lemasters JJ. Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. Mol Pharmacol. 2002;62(1):22-9.
146. Cour M, Loufouat J, Paillard M, Augeul L, Goudable J, Ovize M, Argaud L. Inhibition of mitochondrial permeability transition to prevent the post-cardiac arrest syndrome: a pre-clinical study. Eur Heart J. 2011;32(2):226-35.
147. Jahandiez V, Cour M, Bochaton T, Abrial M, Loufouat J, Gharib A, Varennes A, Ovize M, Argaud L. Fast therapeutic hypothermia prevents post-cardiac arrest syndrome through cyclophilin D-mediated mitochondrial permeability transition inhibition. Basic Res Cardiol. 2017;112(4):35
148. Readnower RD, Pandya JD, McEwen ML, Pauly JR, Springer JE, Sullivan PG. Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats. J Neurotrauma. 2011;28(9):1845-53.
149. Mbye LH, Singh IN, Sullivan PG, Springer JE, Hall ED. Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog. Exp Neurol. 2008;209(1):243-53.
150. 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(4):363.
151. Lin HC, Lee TK, Tsai CC, Lai IR, Lu KS. Ischemic postconditioning protects liver from ischemia-reperfusion injury by modulating mitochondrial permeability transition. Transplantation. 2012;93(3):265-71.
152. Gomez L, Thibault H, Gharib A, Dumont JM, 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(3):H1654-61
153. Clarke SJ, McStay GP, Halestrap AP. 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(38):34793-9
154. Siemion IZ, Pedyczak A, Trojnar J, Zimecki M, Wieczorek Z. Immunosuppressive activity of antamanide and some of its analogues. Peptides. 1992;13(6):1233-7
155. Azzolin L, Antolini N, Calderan A, Ruzza P, Sciacovelli M, Marin O, Mammi S, Bernardi P, Rasola A. Antamanide, a derivative of Amanita phalloides, is a novel inhibitor of the mitochondrial permeability transition pore. PLoS One. 2011 ;6(1):e16280
156. Ahmed-Belkacem A, Colliandre L, Ahnou N, Nevers Q, Gelin M, Bessin Y, Brillet R, Cala O, Douguet D, Bourguet W, Krimm I, Pawlotsky JM, Guichou JF. Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities. Nat Commun. 2016 Sep 22;7:12777.
157. Shore ER, Awais M, Kershaw NM, Gibson RR, Pandalaneni S, Latawiec D, Wen L, Javed MA, Criddle DN, Berry N, O'Neill PM, Lian LY, Sutton R. Small Molecule Inhibitors of Cyclophilin D To Protect Mitochondrial Function as a Potential Treatment for Acute Pancreatitis. J Med Chem. 2016;59(6):2596-611
158. Xie L, Cheng L, Xu G, Zhang J, Ji X, Song E. The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation. Biochem Biophys Res Commun. 2017;487(4):807-812
159. Valasani KR, Sun Q, Fang D, Zhang Z, Yu Q, Guo Y, Li J, Roy A, ShiDu Yan S. Identification of a Small Molecule Cyclophilin D Inhibitor for Rescuing Aβ-Mediated Mitochondrial Dysfunction. ACS Med Chem Lett. 2016;7(3):294-9
160. Zorov DB, Juhaszova M, Yaniv Y, Nuss HB, Wang S, Sollott SJ. Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovasc Res. 2009;83(2):213-25
161. Leducq N, Bono F, Sulpice T, Vin V, Janiak P, Fur GL et al. Role of peripheral benzodiazepine receptors in mitochondrial, cellular, and cardiac damage induced by oxidative stress and ischemia-reperfusion. J Pharmacol Exp Ther. 2003;306(3):828-837.
162. Obame FN, Zini R, Souktani R, Berdeaux A, Morin D. Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization. J Pharmacol Exp Ther. 2007;323(1):336-345.
163. Bordet T, Buisson B, Michaud M, Drouot C, Galéa P, Delaage P, Akentieva NP, Evers AS, Covey DF, Ostuni MA, Lacapère JJ, Massaad C, Schumacher M, Steidl EM, Maux D, Delaage M, Henderson CE, Pruss RM. 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(2):709-20.
164. Schaller S, Paradis S, Ngoh GA, Assaly R, Buisson B, Drouot C, Ostuni MA, Lacapere JJ, Bassissi F, Bordet T, Berdeaux A, Jones SP, Morin D, Pruss RM. TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition. J Pharmacol Exp Ther. 2010;333(3):696-706.
165. Šileikytė J, Blachly-Dyson E, Sewell R, Carpi A, Menabò 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 (Translocator Protein of 18 kDa (TSPO)). J Biol Chem. 2014;289(20):13769-81.
166. Paradis S, Leoni V, Caccia C, Berdeaux A, Morin D. Cardioprotection by the TSPO ligand 4'-chlorodiazepam is associated with inhibition of mitochondrial accumulation of cholesterol at reperfusion. Cardiovasc Res. 2013;98(3):420-7.
167. Musman J, Paradis S, Panel M, Pons S, Barau C, Caccia C, Leoni V, Ghaleh B, Morin D. A TSPO ligand prevents mitochondrial sterol accumulation and dysfunction during myocardial ischemia-reperfusion in hypercholesterolemic rats. Biochem Pharmacol. 2017 Jun 21. pii: S0006-2952(17)30449-5.
168. Le Lamer S, Paradis S, Rahmouni H, Chaimbault C, Michaud M, Culcasi M, Afxantidis J, Latreille M, Berna P, Berdeaux A, Pietri S, Morin D, Donazzolo Y, Abitbol JL, Pruss RM, Schaller S. Translation of TRO40303 from myocardial infarction models to demonstration of safety and tolerance in a randomized Phase I trial. J Transl Med. 2014 Feb 7;12:38.
169. Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P, Cuvier V, Danchin N, Dubois-Randé JL, Engblom H, Erlinge D, Firat H, Halvorsen S, Hansen HS, Hauke W, Heiberg E, Koul S, Larsen AI, Le Corvoisier P, Nordrehaug JE, Paganelli F, Pruss RM, Rousseau H, Schaller S, Sonou G, Tuseth V, Veys J, Vicaut E, Jensen SE. Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. Eur Heart J. 2015;36(2):112-9.
170. Fontaine E, Ichas F, Bernardi P. A ubiquinone-binding site regulates the mitochondrial permeability transition pore. J Biol Chem. 1998;273(40):25734-40.
171. Walter L, Nogueira V, Leverve X, Heitz MP, Bernardi P, Fontaine E. Three classes of ubiquinone analogs regulate the mitochondrial permeability transition pore through a common site. J Biol Chem. 2000;275(38):29521-7.
172. Takeo S, Tanonaka K, Tazuma Y, Miyake K, Murai R. Possible mechanism by which coenzyme Q10 improves reoxygenation-induced recovery of cardiac contractile force after hypoxia. J Pharmacol Exp Ther. 1987;243(3):1131-8.
173. Singh RB, Wander GS, Rastogi A, Shukla PK, Mittal A, Sharma JP, Mehrotra SK, Kapoor R, Chopra RK. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther.1998;12(4):347-53.
174. 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 PG, 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(12):5333-47.
175. Martin LJ, Fancelli D, Wong M, Niedzwiecki M, Ballarini M, Plyte S, Chang Q. GNX-4728, a novel small molecule drug inhibitor of mitochondrial permeability transition, is therapeutic in a mouse model of amyotrophic lateral sclerosis. Front Cell Neurosci. 2014 Dec 19;8:433.
176. Richardson AP, Halestrap AP. Quantification of active mitochondrial permeability transition pores using GNX-4975 inhibitor titrations provides insights into molecular identity. Biochem J. 2016;473(9):1129-40.
177. Roy S, Šileikytė J, Schiavone M, Neuenswander B, Argenton F, Aubé J, Hedrick MP, Chung TD, Forte MA, Bernardi P, Schoenen FJ. Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore. ChemMedChem. 2015;10(10):1655-71.
178. Roy S, Šileikytė J, Neuenswander B, Hedrick MP, Chung TD, Aubé J, Schoenen FJ, Forte MA, Bernardi P. N-Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore. ChemMedChem. 2016;11(3):283-8.
179. Briston T, Lewis S, Koglin M, Mistry K, Shen Y, Hartopp N, Katsumata R, Fukumoto H, Duchen MR, Szabadkai G, Staddon JM, Roberts M, Powney B. Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria. Sci Rep. 2016 Nov 25;6:37798.
180. Daugas E.; Susin S.A.; Zamzami N.; Ferri K.F.; Irinopoulou T.; Larochette N.; Prévost, M.C.; Leber B.; Andrews D.; Penninger J.; Kroemer G. Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis. FASEB J., 2000;14(5):729-739.
181. Li L.Y.; Luo X.; Wang X. Endonuclease G is an apoptotic DNase when released from mitochondria. Nature, 2001;412(6842): 95-99.
182. Spierings D.; McStay G.; Saleh M.; Bender C.; Chipuk J.; Maurer U.; Green DR. Connected to death: the (unexpurgated) mitochondrial pathway of apoptosis. Science. 2005;310(5745):66-67.
183. Kinnally, K.W.; Antonsson, B. A tale of two mitochondrial channels, MAC and PTP, in apoptosis. Apoptosis. 2007;12(5): 857-868.
184. Peixoto PM, Dejean LM, Kinnally KW. The therapeutic potential of mitochondrial channels in cancer, ischemia-reperfusion injury, and neurodegeneration. Mitochondrion. 2012;12(1):14-23.
185. Hattori R.; Hernandez T.E.; Zhu L.; Maulik N.; Otani H.; Kaneda Y.; Das D.K. An essential role of the antioxidant gene Bcl-2 in myocardial adaptation to ischemia: an insight with antisense Bcl-2 therapy. Antioxid. Redox Signal. 2001;3(3):403-413.
186. Chen Z.; Chua C.C.; Ho Y.S.; Hamdy R.C.; Chua B.H. Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice. Am. J. Physiol. Heart Circ Physiol. 2001;280(5):H2313-H2320.
187. Hochhauser E.; Kivity S.; Offen D.; Maulik N.; Otani H.; Barhum Y.; Pannet H.; Shneyvays V.; Shainberg A.; Goldshtaub V.; Tobar A.. Vidne B.A. Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice. Am J Physiol Heart Circ Physiol. 2003;284(6);H2351-H2359.
188. Gustafsson AB, Tsai JG, Logue SE, Crow MT, Gottlieb RA. Apoptosis repressor with caspase recruitment domain protects against cell death by interfering with Bax activation. J Biol Chem. 2004;279(20):21233-21238.
189. Huang J.; Nakamura K.; Ito Y.; Uzuka T.; Morikawa M.; Hirai S.; Tomihara K.; Tanaka T.; Masuta Y.; Ishii K.; Kato K.; Hamada H. Bcl-xL gene transfer inhibits Bax translocation and prolongs cardiac cold preservation time in rats. Circulation. 2005;112(1):76-83.
190. Bombrun A.; Gerber P.; Casi G.; Terradillos O.; Antonsson B.; Halazy S. 3,6-dibromocarbazole piperazine derivatives of 2-propanol as first inhibitors of cytochrome c release via Bax channel modulation. J Med Chem. 2003;46(21):4365-4368.
191. Sawada M.; Hayes P.; Matsuyama S. Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70. Nat Cell Biol. 2003;5(4):352-357.
192. Hetz C, Vitte PA, Bombrun A, Rostovtseva TK, Montessuit S, Hiver A, Schwarz MK, Church DJ, Korsmeyer SJ, Martinou JC, Antonsson B. Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem. 2005;280(52):42960-70.
193. Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C, Kuwana T, Kurth MJ, Shaw JT, Hinshaw JE, Green DR, Nunnari J. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008;14(2):193-204.
194. Grohm J, Kim SW, Mamrak U, Tobaben S, Cassidy-Stone A, Nunnari J, Plesnila N, Culmsee C Inhibition of Drp1 provides neuroprotection in vitro and in vivo. Cell Death Differ. 2012;19(9):1446-58.
195. Ong SB, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121(18):2012-22.
196. Ishikita A, Matoba T, Ikeda G, Koga J, Mao Y, Nakano K, Takeuchi O, Sadoshima J, Egashira K. Nanoparticle-Mediated Delivery of Mitochondrial Division Inhibitor 1 to the Myocardium Protects the Heart From Ischemia-Reperfusion Injury Through Inhibition of Mitochondria Outer Membrane Permeabilization: A New Therapeutic Modality for Acute Myocardial Infarction. J Am Heart Assoc. 2016;5(7). pii: e003872.
197. Colombini M. VDAC structure, selectivity, and dynamics. Biochim Biophys Acta. 2012;1818(6):1457-65.
198. Roman I, Figys J, Steurs G, Zizi M. Hunting interactomes of a membrane protein: obtaining the largest set of voltage-dependent anion channel-interacting protein epitopes. Mol Cell Proteomics. 2006;5(9):1667-80.
199. Shimizu S, Narita M, Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 1999;399(6735):483-7
200. Madesh M.; Hajnóczky G. VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J. Cell. Biol., 2001, 155(6), 1003-1015
201. Shoshan-Barmatz V, Krelin Y, Chen Q. VDAC1 as a player in mitochondria-mediated apoptosis and target for modulating apoptosis. Curr Med Chem. 2017 Jun 16. doi: 10.2174/0929867324666170616105200.
202. Das S, Steenbergen C, Murphy E Does the voltage dependent anion channel modulate cardiac ischemia-reperfusion injury? Biochim Biophys Acta. 2012;1818(6):1451-6.
203. Cheng, E.H.; Sheiko, T.V.; Fisher, J.K.; Craigen, W.J.; Korsmeyer, S.J. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science. 2003;301(5632):513-517.
204. Shimizu, S.; Konishi, A.; Kodama, T.; Tsujimoto, Y. BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death. Proc Natl Acad Sci U S A. 2000;97(7):3100-05.
205. Ono M, Sawa Y, Ryugo M, Alechine AN, Shimizu S, Sugioka R, Tsujimoto Y, Matsuda H. BH4 peptide derivative from Bcl-xL attenuates ischemia/reperfusion injury thorough anti-apoptotic mechanism in rat hearts. Eur J Cardiothorac Surg. 2005;27(1):117-21.
206. Hausenloy DJ, Garcia-Dorado D, Bøtker HE, Davidson SM, Downey J, Engel FB, Jennings R, Lecour S, Leor J, Madonna R, Ovize M, Perrino C, Prunier F, Schulz R, Sluijter JPG, Van Laake LW, Vinten-Johansen J, Yellon DM, Ytrehus K, Heusch G, Ferdinandy P. Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart. Cardiovasc Res. 2017;113(6):564-585