Skip to main content
Log in

Regulation of hexokinase binding to VDAC

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Hexokinase isoforms I and II bind to mitochondrial outer membranes in large part by interacting with the outer membrane voltage-dependent anion channel (VDAC). This interaction results in a shift in the susceptibility of mitochondria to pro-apoptotic signals that are mediated through Bcl2-family proteins. The upregulation of hexokinase II expression in tumor cells is thought to provide both a metabolic benefit and an apoptosis suppressive capacity that gives the cell a growth advantage and increases its resistance to chemotherapy. However, the mechanisms responsible for the anti-apoptotic effect of hexokinase binding and its regulation remain poorly understood. We hypothesize that hexokinase competes with Bcl2 family proteins for binding to VDAC to influence the balance of pro-and anti-apoptotic proteins that control outer membrane permeabilization. Hexokinase binding to VDAC is regulated by protein kinases, notably glycogen synthase kinase (GSK)-3β and protein kinase C (PKC)-ɛ. In addition, there is evidence that the cholesterol content of the mitochondrial membranes may contribute to the regulation of hexokinase binding. At the same time, VDAC associated proteins are critically involved in the regulation of cholesterol uptake. A better characterization of these regulatory processes is required to elucidate the role of hexokinases in normal tissue function and to apply these insights for optimizing cancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abu-Hamad S, Sivan S, Shoshan-Barmatz V (2006) The expression level of the voltage-dependent anion channel controls life and death of the cell. Proc Natl Acad Sci USA 103:5787–5792

    Article  CAS  Google Scholar 

  • Abu-Hamad S, Zaid H, Israelson A, Nahon E, Shoshan-Barmatz V (2008) Hexokinase-I protection against apoptotic cell death is mediated via interaction with the voltage-dependent anion channel-1: mapping the site of binding. J Biol Chem 283:13482–13490

    Article  CAS  Google Scholar 

  • Affaitati A, Cardone L, de Cristofaro T, Carlucci A, Ginsberg MD, Varrone S, Gottesman ME, Avvedimento EV, Feliciello A (2003) Essential role of A-kinase anchor protein 121 for cAMP signaling to mitochondria. J Biol Chem 278:4286–4294

    Article  CAS  Google Scholar 

  • Aflalo C, Azoulay H (1998) Binding of rat brain hexokinase to recombinant yeast mitochondria: effect of environmental factors and the source of porin. J Bioenerg Biomembr 30:245–255

    Article  CAS  Google Scholar 

  • Al Jamal JA (2005) Involvement of porin N,N-dicyclohexylcarbodiimide-reactive domain in hexokinase binding to the outer mitochondrial membrane. Protein J 24:1–8

    Article  CAS  Google Scholar 

  • Arden C, Baltrusch S, Agius L (2006) Glucokinase regulatory protein is associated with mitochondria in hepatocytes. FEBS Lett 580:2065–2070

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Baggetto LG, Clottes E, Vial C (1992) Low mitochondrial proton leak due to high membrane cholesterol content and cytosolic creatine kinase as two features of the deviant bioenergetics of Ehrlich and AS30-D tumor cells. Cancer Res 52:4935–4941

    CAS  Google Scholar 

  • Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (2003) Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92:873–880

    Article  CAS  Google Scholar 

  • Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW et al (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658–662

    Article  CAS  Google Scholar 

  • Basso E, Fante L, Fowlkes J, Petronilli V, Forte MA, Bernardi P (2005) Properties of the permeability transition pore in mitochondria devoid of cyclophilin D. J Biol Chem 280:18558–18561

    Article  CAS  Google Scholar 

  • Bauer MK, Schubert A, Rocks O, Grimm S (1999) Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis. J Cell Biol 147:1493–1502

    Article  CAS  Google Scholar 

  • Bera AK, Ghosh S, Das S (1995) Mitochondrial VDAC can be phosphorylated by cyclic AMP-dependent protein kinase. Biochem Biophys Res Commun 209:213–217

    Article  CAS  Google Scholar 

  • Bijur GN, Jope RS (2003) Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem 87:1427–1435

    Article  CAS  Google Scholar 

  • Bose HS, Baldwin MA, Miller WL (2000a) Evidence that StAR and MLN64 act on the outer mitochondrial membrane as molten globules. Endocr Res 26:629–637

    Article  CAS  Google Scholar 

  • Bose HS, Whittal RM, Huang MC, Baldwin MA, Miller WL (2000b) N-218 MLN64, a protein with StAR-like steroidogenic activity, is folded and cleaved similarly to StAR. Biochemistry 39:11722–11731

    Article  CAS  Google Scholar 

  • Bose M, Whittal RM, Miller WL, Bose HS (2008) Steroidogenic activity of StAR requires contact with mitochondrial VDAC1 and phosphate carrier protein. J Biol Chem 283:8837–8845

    Article  CAS  Google Scholar 

  • Brdiczka D, Kaldis P, Wallimann T (1994) In vitro complex formation between the octamer of mitochondrial creatine kinase and porin. J Biol Chem 269:27640–27644

    CAS  Google Scholar 

  • Brdiczka D, Beutner G, Ruck A, Dolder M, Wallimann T (1998) The molecular structure of mitochondrial contact sites. Their role in regulation of energy metabolism and permeability transition. Biofactors 8:235–242

    CAS  Google Scholar 

  • Broekemeier KM, Dempsey ME, Pfeiffer DR (1989) Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. J Biol Chem 264:7826–7830

    CAS  Google Scholar 

  • Campbell AM, Chan SH (2007) The voltage dependent anion channel affects mitochondrial cholesterol distribution and function. Arch Biochem Biophys 466:203–210

    Article  CAS  Google Scholar 

  • Casadio R, Jacoboni I, Messina A, De Pinto V (2002) A 3D model of the voltage-dependent anion channel (VDAC). FEBS Lett 520:1–7

    Article  CAS  Google Scholar 

  • Chevrollier A, Loiseau D, Chabi B, Renier G, Douay O, Malthiery Y, Stepien G (2005) ANT2 isoform required for cancer cell glycolysis. J Bioenerg Biomembr 37:307–316

    Article  CAS  Google Scholar 

  • Chiara F, Castellaro D, Marin O, Petronilli V, Brusilow WS, Juhaszova M, Sollott SJ, Forte M, Bernardi P, Rasola A (2008) Hexokinase II detachment from mitochondria triggers apoptosis through the permeability transition pore independent of voltage-dependent anion channels. PLoS ONE 3:e1852

    Article  CAS  Google Scholar 

  • Colell A, Garcia-Ruiz C, Lluis JM, Coll O, Mari M, Fernandez-Checa JC (2003) Cholesterol impairs the adenine nucleotide translocator-mediated mitochondrial permeability transition through altered membrane fluidity. J Biol Chem 278:33928–33935

    Article  CAS  Google Scholar 

  • Colombini M (2004) VDAC: the channel at the interface between mitochondria and the cytosol. Mol Cell Biochem 256–257:107–115

    Article  Google Scholar 

  • Crompton M, Barksby E, Johnson N, Capano M (2002) Mitochondrial intermembrane junctional complexes and their involvement in cell death. Biochimie 84:143–152

    Article  CAS  Google Scholar 

  • Danial NN, Gramm CF, Scorrano L, Zhang CY, Krauss S, Ranger AM, Datta SR, Greenberg ME, Licklider LJ, Lowell BB et al (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424:952–956

    Article  CAS  Google Scholar 

  • DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11–20

    Article  CAS  Google Scholar 

  • Distler AM, Kerner J, Hoppel CL (2007) Post-translational modifications of rat liver mitochondrial outer membrane proteins identified by mass spectrometry. Biochim Biophys Acta 1774:628–636

    CAS  Google Scholar 

  • Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM et al (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 64:3892–3899

    Article  CAS  Google Scholar 

  • Fiek C, Benz R, Roos N, Brdiczka D (1982) Evidence for identity between the hexokinase-binding protein and the mitochondrial porin in the outer membrane of rat liver mitochondria. Biochim Biophys Acta 688:429–440

    Article  CAS  Google Scholar 

  • Goldin N, Arzoine L, Heyfets A, Israelson A, Zaslavsky Z, Bravman T, Bronner V, Notcovich A, Shoshan-Barmatz V, Flescher E (2008) Methyl jasmonate binds to and detaches mitochondria-bound hexokinase. Oncogene, Apr 14. doi:10.1038/onc.2008.108

  • Goncalves RP, Buzhynskyy N, Prima V, Sturgis JN, Scheuring S (2007) Supramolecular assembly of VDAC in native mitochondrial outer membranes. J Mol Biol 369:413–418

    Article  CAS  Google Scholar 

  • 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 15:1406–14018

    Article  CAS  Google Scholar 

  • Halestrap AP, Brennerb C (2003) The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr Med Chem 10:1507–1525

    Article  CAS  Google Scholar 

  • Hardwick M, Fertikh D, Culty M, Li H, Vidic B, Papadopoulos V (1999) Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol. Cancer Res 59:831–842

    CAS  Google Scholar 

  • Hashimoto M, Wilson JE (2000) Membrane potential-dependent conformational changes in mitochondrially bound hexokinase of brain. Arch Biochem Biophys 384:163–173

    Article  CAS  Google Scholar 

  • Hauet T, Yao ZX, Bose HS, Wall CT, Han Z, Li W, Hales DB, Miller WL, Culty M, Papadopoulos V (2005) Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into Leydig cell mitochondria. Mol Endocrinol 19:540–554

    Article  CAS  Google Scholar 

  • Hoogenboom BW, Suda K, Engel A, Fotiadis D (2007) The supramolecular assemblies of voltage-dependent anion channels in the native membrane. J Mol Biol 370:246–255

    Article  CAS  Google Scholar 

  • Huang LJ, Wang L, Ma Y, Durick K, Perkins G, Deerinck TJ, Ellisman MH, Taylor SS (1999) NH2-Terminal targeting motifs direct dual specificity A-kinase-anchoring protein 1 (D-AKAP1) to either mitochondria or endoplasmic reticulum. J Cell Biol 145:951–959

    Article  CAS  Google Scholar 

  • Jaburek M, Costa AD, Burton JR, Costa CL, Garlid KD (2006) Mitochondrial PKC epsilon and mitochondrial ATP-sensitive K+ channel copurify and coreconstitute to form a functioning signaling module in proteoliposomes. Circ Res 99:878–883

    Article  CAS  Google Scholar 

  • Jope RS, Johnson GV (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29:95–102

    Article  CAS  Google Scholar 

  • Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL et al (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535–1549

    CAS  Google Scholar 

  • Kinnally KW, Zorov DB, Antonenko YN, Snyder SH, McEnery MW, Tedeschi H (1993) Mitochondrial benzodiazepine receptor linked to inner membrane ion channels by nanomolar actions of ligands. Proc Natl Acad Sci USA 90:1374–1378

    Article  CAS  Google Scholar 

  • Korzick DH, Kostyak JC, Hunter JC, Saupe KW (2007) Local delivery of PKCepsilon-activating peptide mimics ischemic preconditioning in aged hearts through GSK-3beta but not F1-ATPase inactivation. Am J Physiol Heart Circ Physiol 293:H2056–H2063

    Article  CAS  Google Scholar 

  • Le Mellay V, Troppmair J, Benz R, Rapp UR (2002) Negative regulation of mitochondrial VDAC channels by C-Raf kinase. BMC Cell Biol 3:14

    Article  Google Scholar 

  • Li H, Papadopoulos V (1998) Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology 139:4991–4997

    Article  CAS  Google Scholar 

  • Li H, Degenhardt B, Tobin D, Yao ZX, Tasken K, Papadopoulos V (2001a) Identification, localization, and function in steroidogenesis of PAP7: a peripheral-type benzodiazepine receptor- and PKA (RIalpha)-associated protein. Mol Endocrinol 15:2211–2228

    Article  CAS  Google Scholar 

  • Li H, Yao Z, Degenhardt B, Teper G, Papadopoulos V (2001b) Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide. Proc Natl Acad Sci USA 98:1267–1272

    Article  CAS  Google Scholar 

  • Lin DT, Lechleiter JD (2002) Mitochondrial targeted cyclophilin D protects cells from cell death by peptidyl prolyl isomerization. J Biol Chem 277:31134–31141

    Article  CAS  Google Scholar 

  • Linden M, Gellerfors P, Nelson BD (1982) Pore protein and the hexokinase-binding protein from the outer membrane of rat liver mitochondria are identical. FEBS Lett 141:189–192

    Article  CAS  Google Scholar 

  • Linseman DA, Butts BD, Precht TA, Phelps RA, Le SS, Laessig TA, Bouchard RJ, Florez-McClure ML, Heidenreich KA (2004) Glycogen synthase kinase-3beta phosphorylates Bax and promotes its mitochondrial localization during neuronal apoptosis. J Neurosci 24:9993–10002

    Article  CAS  Google Scholar 

  • Liu J, Matyakhina L, Han Z, Sandrini F, Bei T, Stratakis CA, Papadopoulos V (2003) Molecular cloning, chromosomal localization of human peripheral-type benzodiazepine receptor and PKA regulatory subunit type 1A (PRKAR1A)-associated protein PAP7, and studies in PRKAR1A mutant cells and tissues. FASEB J 17:1189–1191

    CAS  Google Scholar 

  • Liu J, Rone MB, Papadopoulos V (2006) Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis. J Biol Chem 281:38879–38893

    Article  CAS  Google Scholar 

  • Lucken-Ardjomande S, Montessuit S, Martinou JC (2008) Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes. Cell Death Differ 15:484–493

    Article  CAS  Google Scholar 

  • Ma Y, Taylor S (2002) A 15-residue bifunctional element in D-AKAP1 is required for both endoplasmic reticulum and mitochondrial targeting. J Biol Chem 277:27328–27336

    Article  CAS  Google Scholar 

  • Macanas-Pirard P, Yaacob NS, Lee PC, Holder JC, Hinton RH, Kass GE (2005) Glycogen synthase kinase-3 mediates acetaminophen-induced apoptosis in human hepatoma cells. J Pharmacol Exp Ther 313:780–789

    Article  CAS  Google Scholar 

  • Machida K, Ohta Y, Osada H (2006) Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells. J Biol Chem 281:14314–14320

    Article  CAS  Google Scholar 

  • Majewski N, Nogueira V, Robey RB, Hay N (2004) Akt inhibits apoptosis downstream of BID cleavage via a glucose-dependent mechanism involving mitochondrial hexokinases. Mol Cell Biol 24:730–740

    Article  CAS  Google Scholar 

  • Malia TJ, Wagner G (2007) NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Biochemistry 46:514–525

    Article  CAS  Google Scholar 

  • Mannella CA, Forte M, Colombini M (1992) Toward the molecular structure of the mitochondrial channel, VDAC. J Bioenerg Biomembr 24:7–19

    Article  CAS  Google Scholar 

  • Marzo I, Brenner C, Zamzami N, Jurgensmeier JM, Susin SA, Vieira HL, Prevost MC, Xie Z, Matsuyama S, Reed JC et al (1998) Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science 281:2027–2031

    Article  CAS  Google Scholar 

  • Mathieu AP, Fleury A, Ducharme L, Lavigne P, LeHoux JG (2002a) Insights into steroidogenic acute regulatory protein (StAR)-dependent cholesterol transfer in mitochondria: evidence from molecular modeling and structure-based thermodynamics supporting the existence of partially unfolded states of StAR. J Mol Endocrinol 29:327–345

    Article  CAS  Google Scholar 

  • Mathieu AP, Lavigne P, LeHoux JG (2002b) Molecular modeling and structure-based thermodynamic analysis of the StAR protein. Endocr Res 28:419–423

    Article  CAS  Google Scholar 

  • Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR (2006) Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell 21:749–760

    Article  CAS  Google Scholar 

  • McEnery MW (1992) The mitochondrial benzodiazepine receptor: evidence for association with the voltage-dependent anion channel (VDAC). J Bioenerg Biomembr 24:63–69

    Article  CAS  Google Scholar 

  • McEnery MW, Snowman AM, Trifiletti RR, Snyder SH (1992) Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier. Proc Natl Acad Sci USA 89:3170–3174

    Article  CAS  Google Scholar 

  • McEnery MW, Dawson TM, Verma A, Gurley D, Colombini M, Snyder SH (1993a) Mitochondrial voltage-dependent anion channel. Immunochemical and immunohistochemical characterization in rat brain. J Biol Chem 268:23289–23296

    CAS  Google Scholar 

  • McEnery MW, Snowman AM, Seagar MJ, Copeland TD, Takahashi M (1993b) Immunological characterization of proteins associated with the purified omega-conotoxin GVIA receptor. Ann N Y Acad Sci 707:386–391

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Morrison RS, Kinoshita Y, Johnson MD, Ghatan S, Ho JT, Garden G (2002) Neuronal survival and cell death signaling pathways. Adv Exp Med Biol 513:41–86

    CAS  Google Scholar 

  • Murphy E (2004) Inhibit GSK-3beta or there’s heartbreak dead ahead. J Clin Invest 113:1526–1528

    CAS  Google Scholar 

  • Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, Inohara H, Kubo T, Tsujimoto Y (2005) Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434:652–658

    Article  CAS  Google Scholar 

  • Nakashima RA, Mangan PS, Colombini M, Pedersen PL (1986) Hexokinase receptor complex in hepatoma mitochondria: evidence from N,N′-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC. Biochemistry 25:1015–1021

    Article  CAS  Google Scholar 

  • Nishihara M, Miura T, Miki T, Tanno M, Yano T, Naitoh K, Ohori K, Hotta H, Terashima Y, Shimamoto K (2007) Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection. J Mol Cell Cardiol 43:564–570

    Article  CAS  Google Scholar 

  • Papadopoulos V, Amri H, Boujrad N, Cascio C, Culty M, Garnier M, Hardwick M, Li H, Vidic B, Brown AS et al (1997) Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis. Steroids 62:21–28

    Article  CAS  Google Scholar 

  • Papadopoulos V, Liu J, Culty M (2007) Is there a mitochondrial signaling complex facilitating cholesterol import. Mol Cell Endocrinol 265–266:59–64

    Article  CAS  Google Scholar 

  • Park SS, Zhao H, Mueller RA, Xu Z (2006) Bradykinin prevents reperfusion injury by targeting mitochondrial permeability transition pore through glycogen synthase kinase 3beta. J Mol Cell Cardiol 40:708–716

    Article  CAS  Google Scholar 

  • Parlo RA, Coleman PS (1984) Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. The truncated Krebs cycle and other metabolic ramifications of mitochondrial membrane cholesterol. J Biol Chem 259:9997–10003

    CAS  Google Scholar 

  • Pastorino JG, Hoek JB (2003) Hexokinase II: the integration of energy metabolism and control of apoptosis. Curr Med Chem 10:1535–1551

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Pedersen PL, Mathupala S, Rempel A, Geschwind JF, Ko YH (2002) Mitochondrial bound type II hexokinase: a key player in the growth and survival of many cancers and an ideal prospect for therapeutic intervention. Biochim Biophys Acta 1555:14–20

    Article  CAS  Google Scholar 

  • Plas DR, Thompson CB (2005) Akt-dependent transformation: there is more to growth than just surviving. Oncogene 24:7435–7442

    Article  CAS  Google Scholar 

  • Schubert A, Grimm S (2004) Cyclophilin D, a component of the permeability transition-pore, is an apoptosis repressor. Cancer Res 64:85–93

    Article  CAS  Google Scholar 

  • Schwertz H, Carter JM, Abdudureheman M, Russ M, Buerke U, Schlitt A, Muller-Werdan U, Prondzinsky R, Werdan K, Buerke M (2007) Myocardial ischemia/reperfusion causes VDAC phosphorylation which is reduced by cardioprotection with a p38 MAP kinase inhibitor. Proteomics 7:4579–4588

    Article  CAS  Google Scholar 

  • Shoshan-Barmatz V, Zalk R, Gincel D, Vardi N (2004) Subcellular localization of VDAC in mitochondria and ER in the cerebellum. Biochim Biophys Acta 1657:105–114

    Article  CAS  Google Scholar 

  • Soccio RE, Breslow JL (2003) StAR-related lipid transfer (START) proteins: mediators of intracellular lipid metabolism. J Biol Chem 278:22183–22186

    Article  CAS  Google Scholar 

  • Stachowiak O, Schlattner U, Dolder M, Wallimann T (1998) Oligomeric state and membrane binding behaviour of creatine kinase isoenzymes: implications for cellular function and mitochondrial structure. Mol Cell Biochem 184:141–151

    Article  CAS  Google Scholar 

  • Sun L, Shukair S, Naik TJ, Moazed F, Ardehali H (2008) Glucose phosphorylation and mitochondrial binding are required for the protective effects of hexokinases I and II. Mol Cell Biol 28:1007–1017

    Article  CAS  Google Scholar 

  • Thomson M (2003) Does cholesterol use the mitochondrial contact site as a conduit to the steroidogenic pathway? Bioessays 25:252–258

    Article  CAS  Google Scholar 

  • Tsujimoto Y, Shimizu S (2000) VDAC regulation by the Bcl-2 family of proteins. Cell Death Differ 7:1174–1181

    Article  CAS  Google Scholar 

  • Tsujishita Y, Hurley JH (2000) Structure and lipid transport mechanism of a StAR-related domain. Nat Struct Biol 7:408–414

    Article  CAS  Google Scholar 

  • Watari H, Arakane F, Moog-Lutz C, Kallen CB, Tomasetto C, Gerton GL, Rio MC, Baker ME, Strauss JF 3rd (1997) MLN64 contains a domain with homology to the steroidogenic acute regulatory protein (StAR) that stimulates steroidogenesis. Proc Natl Acad Sci USA 94:8462–8467

    Article  CAS  Google Scholar 

  • Wilson JE (1995) Hexokinases. Rev Physiol Biochem Pharmacol 126:65–198

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Xie G, Wilson JE (1990) Tetrameric structure of mitochondrially bound rat brain hexokinase: a crosslinking study. Arch Biochem Biophys 276:285–293

    Article  CAS  Google Scholar 

  • Zaid H, Abu-Hamad S, Israelson A, Nathan I, Shoshan-Barmatz V (2005) The voltage-dependent anion channel-1 modulates apoptotic cell death. Cell Death Differ 12:751–760

    Article  CAS  Google Scholar 

  • Zalk R, Israelson A, Garty ES, Azoulay-Zohar H, Shoshan-Barmatz V (2005) Oligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria. Biochem J 386:73–83

    Article  CAS  Google Scholar 

  • Zhao Y, Altman BJ, Coloff JL, Herman CE, Jacobs SR, Wieman HL, Wofford JA, Dimascio LN, Ilkayeva O, Kelekar A et al (2007) Glycogen synthase kinase 3alpha and 3beta mediate a glucose-sensitive antiapoptotic signaling pathway to stabilize Mcl-1. Mol Cell Biol 27:4328–4339

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John G. Pastorino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pastorino, J.G., Hoek, J.B. Regulation of hexokinase binding to VDAC. J Bioenerg Biomembr 40, 171–182 (2008). https://doi.org/10.1007/s10863-008-9148-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-008-9148-8

Keywords

Navigation