The role of hexokinase in cardioprotection - Mechanism and potential for translation

British Journal of Pharmacology

Volumn 172, Issue 8, 2015, Pages 2085-2100

  Halestrap, Andrew P ^a   Pereira, Gonçalo C ^a,b   Pasdois, Philippe ^a,c  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c UNIVERSITÉ DE BORDEAUX   (France)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOSPORIN A; CYTOCHROME C; GLUCOSE 6 PHOSPHATE; HEXOKINASE; HEXOKINASE 2; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; SANGLIFEHRIN A; UNCLASSIFIED DRUG; VOLTAGE DEPENDENT ANION CHANNEL 1; CARRIER PROTEIN; MITOCHONDRIAL PERMEABILITY TRANSITION PORE;

APOPTOSIS; BINDING SITE; BIOENERGY; GLYCOGEN ANALYSIS; HEART PROTECTION; HUMAN; ISCHEMIC PRECONDITIONING; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL PERMEABILITY; NONHUMAN; PH; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CARBONYLATION; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REGULATORY MECHANISM; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; ANTAGONISTS AND INHIBITORS; HEART MITOCHONDRION; METABOLISM; MYOCARDIAL REPERFUSION INJURY;

ANIMALS; CYTOCHROMES C; HEXOKINASE; HUMANS; MITOCHONDRIA, HEART; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MYOCARDIAL REPERFUSION INJURY;

EID: 84925872846     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12899     Document Type: Review

References (148)

1. Ala-Rami A, Ylitalo KV, Hassinen IE, (2003). Ischaemic preconditioning and a mitochondrial K-ATP channel opener both produce cardioprotection accompanied by F1F0-ATPase inhibition in early ischaemia. Basic Res Cardiol 98: 250-258.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14: Ion channesl. Br J Pharmacol 170: 1607-1651.
3. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: Transporters. Br J Pharmacol 170: 1706-1796.
4. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013c). The Concise Guide to PHARMACOLOGY 2013/14: Enzymes. Br J Pharmacol 170: 1797-1867.
5. Argaud L, GateauRoesch O, Chalabreysse L, Gomez L, Loufouat J, Thivolet-Bejui F, et al. (2004). Preconditioning delays Ca2+-induced mitochondrial permeability transition. Cardiovasc Res 61: 115-122.
6. Asimakis GK, (1996). Myocardial glycogen depletion cannot explain the cardioprotective effects of ischemic preconditioning in the rat heart. J Mol Cell Cardiol 28: 563-570.
7. Aubert-Foucher E, Font B, Gautheron DC, (1984). Rabbit heart mitochondrial hexokinase: solubilization and general properties. Arch Biochem Biophys 232: 391-399.
8. Azoulay-Zohar H, Israelson A, Abu-Hamad S, Shoshan-Barmatz V, (2004). In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death. Biochem J 377: 347-355.
9. Baines CP, (2009). The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol 104: 181-188.
10. Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, et al. (2003). Protein kinase C epsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92: 873-880.
11. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, et al. (2005). Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434: 658-662.
12. Bernardi P, (2013). The mitochondrial permeability transition pore: a mystery solved? Front Physiol 4: 95.
13. Bernardi P, Vassanelli S, Veronese P, Colonna R, Szabo I, Zoratti M, (1992). Modulation of the mitochondrial permeability transition pore-effect of protons and divalent cations. J Biol Chem 267: 2934-2939.
14. Beutner G, Ruck A, Riede B, Brdiczka D, (1997). Complexes between hexokinase, mitochondrial porin and adenylate translocator in brain: regulation of hexokinase, oxidative phosphorylation and permeability transition pore. Biochem Soc Trans 25: 151-157.
15. Beutner G, Ruck A, Riede B, Brdiczka D, (1998). Complexes between porin, hexokinase, mitochondrial creatine kinase and adenylate translocator display properties of the permeability transition pore. Implication for regulation of permeability transition by the kinases. Biochim Biophys Acta 1368: 7-18.
16. Bhamra GS, Hausenloy DJ, Davidson SM, Carr RD, Paiva M, Wynne AM, et al. (2008). Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening. Basic Res Cardiol 103: 274-284.
17. Bonora M, Wieckowski MR, Chinopoulos C, Kepp O, Kroemer G, Galluzzi L, et al. (2014). Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition. Oncogene doi: 10.1038/onc.2014.96. [Epub ahead of print].
18. Borutaite V, Budriunaite A, Morkuniene R, Brown GC, (2001). Release of mitochondrial cytochrome c and activation of cytosolic caspases induced by myocardial ischaemia. Biochim Biophys Acta 1537: 101-109.
19. Brdiczka D, (1991). Contact sites between mitochondrial envelope membranes-structure and function in energy-transfer and protein-transfer. Biochim Biophys Acta 1071: 291-312.
20. Brdiczka DG, Zorov DB, Sheu SS, (2006). Mitochondrial contact sites: their role in energy metabolism and apoptosis. Biochim Biophys Acta 1762: 148-163.
21. Budas GR, Churchill EN, Mochly-Rosen D, (2007). Cardioprotective mechanisms of PKC isozyme-selective activators and inhibitors in the treatment of ischemia-reperfusion injury. Pharmacol Res 55: 523-536.
22. Calvert JW, Gundewar S, Jha S, Greer JJ, Bestermann WH, Tian R, et al. (2008). Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling. Diabetes 57: 696-705.
23. Campanella M, Casswell E, Chong S, Farah Z, Wieckowski MR, Abramov AY, et al. (2008). Regulation of mitochondrial structure and function by the F1F0-ATPase inhibitor protein, IF1. Cell Metab 8: 13-25.
24. Campanella M, Parker N, Tan CH, Hall AM, Duchen MR, (2009). IF(1): setting the pace of the F(1)F(o)-ATP synthase. Trends Biochem Sci 34: 343-350.
25. Chiara F, Castellaro D, Marin O, Petronilli V, Brusilow WS, Juhaszova M, et al. (2008). Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltage-dependent anion channels. PLoS ONE 3: e1852.
26. Clarke SJ, McStay GP, Halestrap AP, (2002). 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 277: 34793-34799.
27. Clarke SJ, Khaliulin I, Das M, Parker JE, Heesom KJ, Halestrap AP, (2008). 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 102: 1082-1090.
28. Colombini M, (2012). VDAC structure, selectivity, and dynamics. Biochim Biophys Acta 1818: 1457-1465.
29. Connern CP, Halestrap AP, (1996). Chaotropic agents and increased matrix volume enhance binding of mitochondrial cyclophilin to the inner mitochondrial membrane and sensitise the mitochondrial permeability transition to [Ca2+]. Biochemistry 35: 8172-8180.
30. Cross HR, Opie LH, Radda GK, Clarke K, (1996). Is a high glycogen content beneficial or detrimental to the ischemic rat heart? A controversy resolved. Circ Res 78: 482-491.
31. Da Silva D, Ausina P, Alencar EM, Coelho WS, Zancan P, Sola-Penna M, (2012). Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice. IUBMB Life 64: 766-774.
32. Di Lisa F, Carpi A, Giorgio V, Bernardi P, (2011). The mitochondrial permeability transition pore and cyclophilin D in cardioprotection. Biochim Biophys Acta 1813: 1316-1322.
33. Disatnik MH, Ferreira JC, Campos JC, Gomes KS, Dourado PM, Qi X, et al. (2013). Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction. J Am Heart Assoc 2: e000461.
34. Dolder M, Walzel B, Speer O, Schlattner U, Wallimann T, (2003). Inhibition of the mitochondrial permeability transition by creatine kinase substrates-requirement for microcompartmentation. J Biol Chem 278: 17760-17766.
35. Doran E, Halestrap AP, (2000). Cytochrome c release from isolated rat liver mitochondria can occur independently of outer-membrane rupture: possible role of contact sites. Biochem J 348: 343-350.
36. Finegan BA, Lopaschuk GD, Gandhi M, Clanachan AS, (1995). Ischemic preconditioning inhibits glycolysis and proton production in isolated working rat hearts. Am J Physiol 269: H1767-H1775.
37. Fullmer TM, Pei S, Zhu Y, Sloan C, Manzanares R, Henrie B, et al. (2013). Insulin suppresses ischemic preconditioning-mediated cardioprotection through Akt-dependent mechanisms. J Mol Cell Cardiol 64: 20-29.
38. Gao D, Zhang L, Dhillon R, Hong TT, Shaw RM, Zhu J, (2013). Dynasore protects mitochondria and improves cardiac lusitropy in Langendorff perfused mouse heart. PLoS ONE 8: e60967.
39. Gelb BD, Adams V, Jones SN, Griffin LD, MacGregor GR, McCabe ERB, (1992). Targeting of hexokinase-1 to liver and hepatoma mitochondria. Proc Natl Acad Sci U S A 89: 202-206.
40. Giorgio V, Bisetto E, Soriano ME, Dabbeni-Sala F, Basso E, Petronilli V, et al. (2009). Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting with the lateral stalk of the complex. J Biol Chem 284: 33982-33988.
41. Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, et al. (2013). Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A 110: 5887-5892.
42. Gomez L, Li B, Mewton N, Sanchez I, Piot C, Elbaz M, et al. (2009). Inhibition of mitochondrial permeability transition pore opening: translation to patients. Cardiovasc Res 83: 226-233.
43. Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N, (2001). Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 15: 1406-1418.
44. Green DW, Murray HN, Sleph PG, Wang FL, Baird AJ, Rogers WL, et al. (1998). Preconditioning in rat hearts is independent of mitochondrial F1F0 ATPase inhibition. Am J Physiol 274: H90-H97.
45. Griffiths EJ, Halestrap AP, (1995). Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J 307: 93-98.
46. Grover GJ, Atwal KS, Sleph PG, Wang FL, Monshizadegan H, Monticello T, et al. (2004). Excessive ATP hydrolysis in ischemic myocardium by mitochondrial F1F0-ATPase: effect of selective pharmacological inhibition of mitochondrial ATPase hydrolase activity. Am J Physiol 287: H1747-H1755.
47. Gurel E, Smeele KM, Eerbeek O, Koeman A, Demirci C, Hollmann MW, et al. (2009). Ischemic preconditioning affects hexokinase activity and HKII in different subcellular compartments throughout cardiac ischemia-reperfusion. J Appl Physiol 106: 1909-1916.
48. Gurel E, Ustunova S, Kapucu A, Yilmazer N, Eerbeek O, Nederlof R, et al. (2013). Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart. Mol Biol Rep 40: 4153-4160.
49. Halestrap AP, (1991). Calcium-dependent opening of a non-specific pore in the mitochondrial inner membrane is inhibited at pH values below 7-implications for the protective effect of low pH against chemical and hypoxic cell damage. Biochem J 278: 715-719.
50. Halestrap AP, (2009). What is the mitochondrial permeability transition pore? J Mol Cell Cardiol 46: 821-831.
51. Halestrap AP, (2010). A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection. Biochem Soc Trans 38: 841-860.
52. Halestrap AP, Pasdois P, (2009). The role of the mitochondrial permeability transition pore in heart disease. Biochim Biophys Acta 1787: 1402-1415.
53. Halestrap AP, Connern CP, Griffiths EJ, Kerr PM, (1997). Cyclosporin A binding to mitochondrial cyclophilin inhibits the permeability transition pore and protects hearts from ischaemia/reperfusion injury. Mol Cell Biochem 174: 167-172.
54. Halestrap AP, Kerr PM, Javadov S, Woodfield KY, (1998). Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart. Biochim Biophys Acta 1366: 79-94.
55. Halestrap AP, Clarke SJ, Javadov SA, (2004). Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc Res 61: 372-385.
56. Halestrap AP, Clarke SJ, Khaliulin I, (2007). The role of mitochondria in protection of the heart by preconditioning. Biochim Biophys Acta 1767: 1007-1031.
57. Hall AR, Burke N, Dongworth RK, Hausenloy DJ, (2014). Mitochondrial fusion and fission proteins: novel therapeutic targets for combating cardiovascular disease. Br J Pharmacol 171: 1890-1906.
58. Hausenloy DJ, Yellon DM, (2006). Survival kinases in ischemic preconditioning and postconditioning. Cardiovasc Res 70: 240-253.
59. Hausenloy DJ, Yellon DM, (2011). The therapeutic potential of ischemic conditioning: an update. Nat Rev Cardiol 8: 619-629.
60. Hausenloy DJ, Ong SB, Yellon DM, (2009). The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol 104: 189-202.
61. Hausenloy DJ, Boston-Griffiths E, Yellon DM, (2012). Cardioprotection during cardiac surgery. Cardiovasc Res 94: 253-265.
62. Huang JH, Ito Y, Morikawa M, Uchida H, Kobune M, Sasaki K, et al. (2003). Bcl-xL gene transfer protects the heart against ischemia/reperfusion injury. Biochem Biophys Res Commun 311: 64-70.
63. Inserte J, Hernando V, Garcia-Dorado D, (2012). Contribution of calpains to myocardial ischemia/reperfusion injury. Cardiovasc Res 96: 23-31.
64. Javadov SA, Clarke S, Das M, Griffiths EJ, Lim KHH, Halestrap AP, (2003). Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart. J Physiol 549: 513-524.
65. Jennings RB, Reimer KA, Steenbergen C, (1991). Effect of inhibition of the mitochondrial ATPase on net myocardial ATP in total ischemia. J Mol Cell Cardiol 23: 1383-1395.
66. Jennings RB, Sebbag L, Schwartz LM, Crago MS, Reimer KA, (2001). Metabolism of preconditioned myocardium: effect of loss and reinstatement of cardioprotection. J Mol Cell Cardiol 33: 1571-1588.
67. Jiang S, Zhang LF, Zhang HW, Hu S, Lu MH, Liang S, et al. (2012). A novel miR-155/miR-143 cascade controls glycolysis by regulating hexokinase 2 in breast cancer cells. EMBO J 31: 1985-1998.
68. Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, et al. (2004). Glycogen synthase kinase-3 beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113: 1535-1549.
69. Juhaszova M, Zorov DB, Yaniv Y, Nuss HB, Wang S, Sollott SJ, (2009). Role of glycogen synthase kinase-3beta in cardioprotection. Circ Res 104: 1240-1252.
70. Karch J, Molkentin JD, (2014). Identifying the components of the elusive mitochondrial permeability transition pore. Proc Natl Acad Sci U S A 111: 10396-10397.
71. Kerner J, Lee K, Tandler B, Hoppel CL, (2012). VDAC proteomics: post-translation modifications. Biochim Biophys Acta 1818: 1520-1525.
72. Kerr PM, Suleiman MS, Halestrap AP, (1999). Reversal of permeability transition during recovery of hearts from ischemia and its enhancement by pyruvate. Am J Physiol 276: H496-H502.
73. Kersten JR, Toller WG, Gross ER, Pagel PS, Warltier DC, (2000). Diabetes abolishes ischemic preconditioning: role of glucose, insulin, and osmolality. Am J Physiol Heart 278: H1218-H1224.
74. Khaliulin I, Schwalb H, Wang P, Houminer E, Grinberg L, Katzeff H, et al. (2004). Preconditioning improves postischemic mitochondrial function and diminishes oxidation of mitochondrial proteins. Free Radic Biol Med 37: 1-9.
75. Khaliulin I, Clarke SJ, Lin H, Parker J, Suleiman M-S, Halestrap AP, (2007). Temperature preconditioning of isolated rat hearts-a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore. J Physiol 581: 1147-1161.
76. Khaliulin I, Parker JE, Halestrap AP, (2010). Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning. Cardiovasc Res 88: 324-333.
77. Khaliulin I, Halestrap AP, Suleiman MS, (2011). Temperature preconditioning is optimal at 26 degrees C and confers additional protection to hypothermic cardioplegic ischemic arrest. Exp Biol Med (Maywood) 236: 736-745.
78. Khaliulin I, Halestrap A, Bryant S, Dudley D, James A, Suleiman M-S, (2014). Clinically-relevant consecutive treatment with isoproterenol and adenosine protects the failing heart against ischaemia and reperfusion. J Transl Med 12: 139.
79. King LM, Opie LH, (1996). Does preconditioning act by glycogen depletion in the isolated rat heart? J Mol Cell Cardiol 28: 2305-2321.
80. Kingsley PB, Sako EY, Yang MQ, Zimmer SD, Ugurbil K, Foker JE, et al. (1991). Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts. Am J Physiol 261: H469-H478.
81. Kloner RA, (2013). Current state of clinical translation of cardioprotective agents for acute myocardial infarction. Circ Res 113: 451-463.
82. Knoll G, Brdiczka D, (1983). Changes in freeze-fractured mitochondrial membranes correlated to their energetic state. Dynamic interactions of the boundary membranes. Biochim Biophys Acta 733: 102-110.
83. Kottke M, Adams V, Wallimann T, Nalam VK, Brdiczka D, (1991). Location and regulation of octameric mitochondrial creatine kinase in the contact sites. Biochim Biophys Acta 1061: 215-225.
84. Laclau MN, Boudina S, Thambo JB, Tariosse L, Gouverneur G, Bonoron-Adele S, et al. (2001). Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase. J Mol Cell Cardiol 33: 947-956.
85. Lesnefsky EJ, Tandler B, Ye JA, Slabe TJ, Turkaly J, Hoppel CL, (1997). Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria. Am J Physiol 273: H1544-H1554.
86. Lim KHH, Javadov SA, Das M, Clarke SJ, Suleiman MS, Halestrap AP, (2002). The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration. J Physiol 545: 961-974.
87. Lim SY, Hausenloy DJ, (2012). Remote ischemic conditioning: from bench to bedside. Front Physiol 3: 27.
88. Lim SY, Davidson SM, Hausenloy DJ, Yellon DM, (2007). Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore. Cardiovasc Res 75: 530-535.
89. Martinou JC, Youle RJ, (2011). Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21: 92-101.
90. Mathupala SP, Ko YH, Pedersen PL, (2009). Hexokinase-2 bound to mitochondria: cancer's stygian link to the 'Warburg Effect' and a pivotal target for effective therapy. Semin Cancer Biol 19: 17-24.
91. McNulty PH, Darling A, Whiting JM, (1996). Glycogen depletion contributes to ischemic preconditioning in the rat heart in vivo. Am J Physiol 271: H2283-H2289.
92. Miyamoto S, Murphy AN, Brown JH, (2008). Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ 15: 521-529.
93. Murphy E, Steenbergen C, (2007). Preconditioning: the mitochondrial connection. Annu Rev Physiol 69: 51-67.
94. Murphy E, Steenbergen C, (2008). Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 88: 581-609.
95. Murry CE, Richard VJ, Reimer KA, Jennings RB, (1990). Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res 66: 913-931.
96. Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, et al. (2005). Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434: 652-658.
97. Neary CL, Pastorino JG, (2013). Akt inhibition promotes hexokinase 2 redistribution and glucose uptake in cancer cells. J Cell Physiol 228: 1943-1948.
98. Nederlof R, Xie C, Eerbeek O, Koeman A, Milstein DM, Hollmann MW, et al. (2013). Pathophysiological consequences of TAT-HKII peptide administration are independent of impaired vascular function and ensuing ischemia. Circ Res 112: e8-e13.
99. Nederlof R, Eerbeek O, Hollmann MW, Southworth R, Zuurbier CJ, (2014). Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart. Br J Pharmacol 171: 2067-2079.
100. Ong S-B, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ, (2010). Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation 121: 2012-2022.
101. Ovize M, Thibault H, Przyklenk K, (2013). Myocardial conditioning: opportunities for clinical translation. Circ Res 113: 439-450.
102. Pasdois P, Parker JC, Griffiths EJ, Halestrap AP, (2011). The role of oxidized cytochrome c in regulating mitochondrial reactive oxygen species production and its perturbation in ischaemia. Biochem J 436: 493-505.
103. Pasdois P, Parker JE, Halestrap AP, (2012). Extent of mitochondrial hexokinase II dissociation during ischemia correlates with mitochondrial cytochrome c release, reactive oxygen species production, and infarct size on reperfusion. J Am Heart Assoc 2: e005645.
104. Pasdois P, Parker JE, Griffiths EJ, Halestrap AP, (2013). Hexokinase II and reperfusion injury TAT-HK2 peptide impairs vascular function in Langendorff-perfused rat hearts. Circ Res 112: e3-e7.
105. Pastorino JG, Hoek JB, (2003). Hexokinase II: the integration of energy metabolism and control of apoptosis. Curr Med Chem 10: 1535-1551.
106. Pastorino JG, Hoek JB, (2008). Regulation of hexokinase binding to VDAC. J Bioenerg Biomembr 40: 171-182.
107. Pastorino JG, Shulga N, Hoek JB, (2002). Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem 277: 7610-7618.
108. Pastorino JG, Hoek JB, Shulga N, (2005). Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res 65: 10545-10554.
109. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucl Acids Res 42 (Database Issue): D1098-D1106.
110. Penso J, Beitner R, (1998). Clotrimazole and bifonazole detach hexokinase from mitochondria of melanoma cells. Eur J Pharmacol 342: 113-117.
111. Perevoshchikova IV, Zorov SD, Kotova EA, Zorov DB, Antonenko YN, (2010). Hexokinase inhibits flux of fluorescently labeled ATP through mitochondrial outer membrane porin. FEBS Lett 584: 2397-2402.
112. Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, et al. (2008). Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359: 473-481.
113. Postic C, Shiota M, Magnuson MA, (2001). Cell-specific roles of glucokinase in glucose homeostasis. Recent Prog Horm Res 56: 195-217.
114. Rauch U, Schulze K, Witzenbichler B, Schultheiss HP, (1994). Alteration of the cytosolic-mitochondrial distribution of high-energy phosphates during global myocardial ischemia may contribute to early contractile failure. Circ Res 75: 760-769.
115. Roberts DJ, Tan-Sah VP, Smith JM, Miyamoto S, (2013). Akt phosphorylates HK-II at Thr-473 and increases mitochondrial HK-II association to protect cardiomyocytes. J Biol Chem 288: 23798-23806.
116. Robey RB, Hay N, (2005). Mitochondrial hexokinases: guardians of the mitochondria. Cell Cycle 4: 654-658.
117. Rodriguez-Sinovas A, Boengler K, Cabestrero A, Gres P, Morente M, Ruiz-Meana M, et al. (2006). Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res 99: 93-101.
118. Schaefer S, Ramasamy R, (1997). Glycogen utilization and ischemic injury in the isolated rat heart. Cardiovasc Res 35: 90-98.
119. Schaller S, Paradis S, Ngoh GA, Assaly R, Buisson B, Drouot C, et al. (2010). TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition. J Pharmacol Exp Ther 333: 696-706.
120. Schulz R, Heusch G, (2006). Connexin43 and ischemic preconditioning. Adv Cardiol 42: 213-227.
121. Sharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, et al. (2014). Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J 28: 316-326.
122. Shoshan-Barmatz V, Mizrachi D, (2012). VDAC1: from structure to cancer therapy. Front Oncol 2: 164.
123. Shoshan-Barmatz V, Zakar M, Rosenthal K, Abu-Hamad S, (2009). Key regions of VDAC1 functioning in apoptosis induction and regulation by hexokinase. Biochim Biophys Acta 1787: 421-430.
124. Sileikyte J, Petronilli V, Zulian A, Dabbeni-Sala F, Tognon G, Nikolov P, et al. (2011). Regulation of the inner membrane mitochondrial permeability transition by the outer membrane translocator protein (peripheral benzodiazepine receptor). J Biol Chem 286: 1046-1053.
125. Sileikyte J, Blachly-Dyson E, Sewell R, Carpi A, Menabo R, Di Lisa F, et al. (2014). Regulation of the mitochondrial permeability transition pore by the outer membrane does not involve the peripheral benzodiazepine receptor (TSPO). J Biol Chem 289: 13769-13781.
126. Smeele KM, Southworth R, Wu R, Xie C, Nederlof R, Warley A, et al. (2011). Disruption of hexokinase II-mitochondrial binding blocks ischemic preconditioning and causes rapid cardiac necrosis. Circ Res 108: 1165-1169.
127. Solskov L, Lofgren B, Kristiansen SB, Jessen N, Pold R, Nielsen TT, et al. (2008). Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration. Basic Clin Pharmacol Toxicol 103: 82-87.
128. Soriano ME, Scorrano L, (2010). The interplay between BCL-2 family proteins and mitochondrial morphology in the regulation of apoptosis. Adv Exp Med Biol 687: 97-114.
129. Speer O, Back N, Buerklen T, Brdiczka D, Koretsky A, Wallimann T, et al. (2005). Octameric mitochondrial creatine kinase induces and stabilizes contact sites between the inner and outer membrane. Biochem J 385: 445-450.
130. Spindler M, Meyer K, Stromer H, Leupold A, Boehm E, Wagner H, et al. (2004). Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. Am J Physiol 287: H1039-H1045.
131. Tait SW, Green DR, (2010). Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11: 621-632.
132. Tomasello MF, Guarino F, Reina S, Messina A, De Pinto V, (2013). The voltage-dependent anion selective channel 1 (VDAC1) topography in the mitochondrial outer membrane as detected in intact cell. PLoS ONE 8: e81522.
133. Tsang A, Hausenloy DJ, Mocanu MM, Carr RD, Yellon DM, (2005). Preconditioning the diabetic heart-the importance of Akt phosphorylation. Diabetes 54: 2360-2364.
134. Vander Heide RS, Delyani JA, Jennings RB, Reimer KA, Steenbergen C, (1996a). Reducing lactate accumulation does not attenuate lethal ischemic injury in isolated perfused rat hearts. Am J Physiol 270: H38-H44.
135. Vander Heide RS, Hill ML, Reimer KA, Jennings RB, (1996b). Effect of reversible ischemia on the activity of the mitochondrial ATPase: relationship to ischemic preconditioning. J Mol Cell Cardiol 28: 103-112.
136. Vogt AM, Ackermann C, Yildiz M, Schoels W, Kubler W, (2002a). Lactate accumulation rather than ATP depletion predicts ischemic myocardial necrosis-implications for the development of lethal myocardial injury. Biochim Biophys Acta 1586: 219-226.
137. Vogt AM, Poolman M, Ackermann C, Yildiz M, Schoels W, Fell DA, et al. (2002b). Regulation of glycolytic flux in ischemic preconditioning-a study employing metabolic control analysis. J Biol Chem 277: 24411-24419.
138. Vuorinen K, Ylitalo K, Peuhkurinen K, Raatikainen P, Alarami A, Hassinen IE, (1995). Mechanisms of ischemic preconditioning in rat myocardium: roles of adenosine, cellular energy state, and mitochondrial F1F0-ATPase. Circulation 91: 2810-2818.
139. Wei L, Zhou Y, Dai Q, Qiao C, Zhao L, Hui H, et al. (2013). Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma. Cell Death Dis 4: e601.
140. Whelan RS, Konstantinidis K, Wei AC, Chen Y, Reyna DE, Jha S, et al. (2012). Bax regulates primary necrosis through mitochondrial dynamics. Proc Natl Acad Sci U S A 109: 6566-6571.
141. Whittington HJ, Hall AR, McLaughlin CP, Hausenloy DJ, Yellon DM, Mocanu MM, (2013). Chronic metformin associated cardioprotection against infarction: not just a glucose lowering phenomenon. Cardiovasc Drugs Ther 27: 5-16.
142. Wilson JE, (2003). Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 206: 2049-2057.
143. Wu R, Smeele KM, Wyatt E, Ichikawa Y, Eerbeek O, Sun L, et al. (2011). Reduction in hexokinase II levels results in decreased cardiac function and altered remodeling after ischemia/reperfusion injury. Circ Res 108: 60-69.
144. Xie GC, Wilson JE, (1988). Rat brain hexokinase: the hydrophobic N-terminus of the mitochondrially bound enzyme is inserted in the lipid bilayer. Arch Biochem Biophys 267: 803-810.
145. Yang X, Cohen MV, Downey JM, (2010). Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc Drugs Ther 24: 225-234.
146. Zepeda R, Kuzmicic J, Parra V, Troncoso R, Pennanen C, Riquelme JA, et al. (2014). Drp1 loss-of-function reduces cardiomyocyte oxygen dependence protecting the heart from ischemia-reperfusion injury. J Cardiovasc Pharmacol 63: 477-487.
147. Zorov DB, Juhaszova M, Sollott SJ, (2006). Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta 1757: 509-517.
148. Zuurbier CJ, Eerbeek O, Meijer AJ, (2005). Ischemic preconditioning, insulin, and morphine all cause hexokinase redistribution. Am J Physiol Heart 289: H496-H499.