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Isoforms of voltage-dependent anion channel of the outer mitochondrial membrane and experimental models to study their physiological role

  • V. V. Teplova
  • I. V. Odinokova
  • E. L. Holmuhamedov
Reviews

Abstract

The review outlines our current understanding of the role of porins, the proteins forming voltage-dependent anion channels (VDAC), in regulation of permeability of the outer mitochondrial membrane. Recent data on the porin structure, amino acid sequence, and isoforms are discussed. The existence of three different VDAC isoforms in mammalian cells suggests that each isoform may play a specific physiological role that remains unknown so far. Different model systems and methods used for studies of functional differences between VDAC isoforms are overviewed. Particular attention is paid to studies of mammalian VDAC isoforms by means of expression of the corresponding genes in yeast and human cells as well as creation of stem cell clones and animals with genetically deficient isoforms of VDAC. It is concluded that permeability of the outer membrane plays a crucial role in the mechanisms of metabolic regulation and that porins are vitally important in the physiology of mammals. The data on the functional role of the VDAC isoforms can be useful for under-standing the mechanisms of such pathologies as cancer, diabetes, and neuromuscular diseases.

Keywords

mitochondria permeability outer membrane porins VDAC isoforms gene expression 

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References

  1. 1.
    Garcia-Rivas G.J., Torre-Amione G. 2009. Abnormal mitochondrial function during ischemia reperfusion provides targets for pharmacological therapy. Methodist. Debakey. Cardiovasc. J. 5, 2–7.PubMedGoogle Scholar
  2. 2.
    Kuznetsov A.V., Hermann M., Saks V., Hengster P., Margreiter R. 2009. The cell-type specificity of mitochondrial dynamics. Int. J. Biochem. Cell Biol. 41, 1928–1939.PubMedCrossRefGoogle Scholar
  3. 3.
    Martinelli P., Rugarli E.I. 2010. Emerging roles of mitochondrial proteases in neurodegeneration. Biochim. Biophys. Acta. 1797, 1–10.PubMedGoogle Scholar
  4. 4.
    Tylkova L. 2009. Architectural and functional remodeling of cardiac and skeletal muscle cells in mice lacking specific isoenzymes of creatine kinase. Gen. Physiol. Biophys. 28, 219–224.PubMedCrossRefGoogle Scholar
  5. 5.
    Antignani A., Youle R.J. 2006. How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane? Curr. Opin. Cell Biol. 18, 685–689.PubMedCrossRefGoogle Scholar
  6. 6.
    Dejean L.M., Martinez-Caballero S., Kinnally K.W. 2006. Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis? Cell Death. Differ. 13, 1387–1395.PubMedCrossRefGoogle Scholar
  7. 7.
    Benz R. 1994. Permeation of hydrophilic solutes through mitochondrial outer membranes: Review on mitochondrial porins. Biochim. Biophys. Acta. 1197, 167–196.PubMedGoogle Scholar
  8. 8.
    Young M.J., Bay D.C., Hausner G., Court D.A. 2007. The evolutionary history of mitochondrial porins. BMC Evol. Biol. 7, 31.PubMedCrossRefGoogle Scholar
  9. 9.
    Colombini M. 2004. VDAC: The channel at the interface between mitochondria and the cytosol. Mol.Cell Biochem. 256-257, 107–115.PubMedCrossRefGoogle Scholar
  10. 10.
    Shoshan-Barmatz V., Israelson A., Brdiczka D., Sheu S.S. 2006. The voltage-dependent anion channel (VDAC): Function in intracellular signalling, cell life and cell death. Curr. Pharm. Des. 12, 2249–2270.PubMedCrossRefGoogle Scholar
  11. 11.
    Vander Heiden M.G., Chandel N.S., Li X.X., Schumacker P.T., Colombini M., Thompson C.B. 2000. Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. Proc. Natl. Acad. Sci. USA. 97, 4666–4671.CrossRefGoogle Scholar
  12. 12.
    Lemasters J.J., Holmuhamedov E. 2006. Voltage-dependent anion channel (VDAC) as mitochondrial governator — thinking outside the box. Biochim. Biophys. Acta. 1762, 181–190.PubMedGoogle Scholar
  13. 13.
    Holmuhamedov E., Lemasters J.J. 2009. Ethanol exposure decreases mitochondrial outer membrane permeability in cultured rat hepatocytes. Arch. Biochem. Biophys. 481, 226–233.PubMedCrossRefGoogle Scholar
  14. 14.
    Rostovtseva T., Colombini M. 1996. ATP flux is controlled by a voltage-gated channel from the mitochondrial outer membrane. J. Biol. Chem. 271, 28006–28008.PubMedCrossRefGoogle Scholar
  15. 15.
    Rostovtseva T., Colombini M. 1997. VDAC channels mediate and gate the flow of ATP: Implications for the regulation of mitochondrial function. Biophys. J. 72, 1954–1962.PubMedCrossRefGoogle Scholar
  16. 16.
    Rostovtseva T.K., Tan W., Colombini M. 2005. On the role of VDAC in apoptosis: Fact and fiction. J. Bioenerg. Biomembr. 37, 129–142.PubMedCrossRefGoogle Scholar
  17. 17.
    Rostovtseva T.K., Bezrukov S.M. 2008. VDAC regulation: Role of cytosolic proteins and mitochondrial lipids. J. Bioenerg. Biomembr. 40, 163–170.PubMedCrossRefGoogle Scholar
  18. 18.
    Tan W., Lai J.C., Miller P., Stein C.A., Colombini M. 2007. Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP. Am. J. Physiol. Cell Physiol. 292, C1388–C1397.PubMedCrossRefGoogle Scholar
  19. 19.
    Schein S.J., Colombini M., Finkelstein A. 1976. Reconstitution in planar lipid bilayers of a voltage-dependent anionselective channel obtained from paramecium mitochondria. J. Membr. Biol. 30, 99–120.PubMedCrossRefGoogle Scholar
  20. 20.
    Colombini M. 1979. A candidate for the permeability pathway of the outer mitochondrial membrane. Nature. 279, 643–645.PubMedCrossRefGoogle Scholar
  21. 21.
    Bayrhuber M., Meins T., Habeck M., Becker S., Giller K., Villinger S., Vonrhein C., Griesinger C., Zweckstetter M., Zeth K. 2008. Structure of the human voltage-dependent anion channel. Proc. Natl. Acad. Sci. USA. 105, 15370–15375.PubMedCrossRefGoogle Scholar
  22. 22.
    Hiller S., Garces R.G., Malia T.J., Orekhov V.Y., Colombini M., Wagner G. 2008. Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science. 321, 1206–1210.PubMedCrossRefGoogle Scholar
  23. 23.
    Ujwal R., Cascio D., Colletier J.P., Faham S., Zhang J., Toro L., Ping P., Abramson J. 2008. The crystal structure of mouse VDAC1 at 2.3 Å resolution reveals mechanistic insights into metabolite gating. Proc. Natl. Acad. Sci. USA. 105, 17742–17747.PubMedCrossRefGoogle Scholar
  24. 24.
    De Pinto V., Tomasello F., Messina A., Guarino F., Benz R., La M.D., Magri A., Milardi D., Pappalardo G. 2007. Determination of the conformation of the human VDAC1 N-terminal peptide, a protein moiety essential for the functional properties of the pore. Chembiochem. 8, 744–756.PubMedCrossRefGoogle Scholar
  25. 25.
    Stanley S., Dias J.A., D’Arcangelis D., Mannella C.A. 1995. Peptide-specific antibodies as probes of the topography of the voltage-gated channel in the mitochondrial outer membrane of Neurospora crassa. J. Biol. Chem. 270, 16694–16700.PubMedCrossRefGoogle Scholar
  26. 26.
    Koppel D.A., Kinnally K.W., Masters P., Forte M., Blachly-Dyson E., Mannella C.A. 1998. Bacterial expression and characterization of the mitochondrial outer membrane channel. Effects of N-terminal modifications. J. Biol. Chem. 273, 13794–13800.PubMedCrossRefGoogle Scholar
  27. 27.
    Popp B., Court D.A, Benz R., Neupert W., Lill R. 1996. The role of the N and C termini of recombinant Neurospora mitochondrial porin in channel formation and voltage-dependent gating. J. Biol. Chem. 271, 13593–13599.PubMedCrossRefGoogle Scholar
  28. 28.
    De Pinto V., Guarino F., Guarnera A., Messina A., Reina S., Tomasello F.M., Palermo V., Mazzoni C. 2010. Characterization of human VDAC isoforms: A peculiar function for VDAC3? Biochim. Biophys. Acta. 1797, 1268–1275.PubMedCrossRefGoogle Scholar
  29. 29.
    De Pinto V., Ludwig O., Krause J., Benz R., Palmieri F. 1987. Porin pores of mitochondrial outer membranes from high and low eukaryotic cells: Biochemical and biophysical characterization. Biochim. Biophys. Acta. 894, 109–119.PubMedCrossRefGoogle Scholar
  30. 30.
    Menzel V.A., Cassara M.C., Benz R., De P., V, Messina A., Cunsolo V., Saletti R., Hinsch K.D., Hinsch E. 2009. Molecular and functional characterization of VDAC2 purified from mammal spermatozoa. Biosci. Rep. 29, 351–362.PubMedCrossRefGoogle Scholar
  31. 31.
    Hinsch K.D., De P., V, Aires V.A., Schneider X., Messina A., Hinsch E. 2004. Voltage-dependent anion-selective channels VDAC2 and VDAC3 are abundant proteins in bovine outer dense fibers, a cytoskeletal component of the sperm flagellum. J. Biol. Chem. 279, 15281–15288.PubMedCrossRefGoogle Scholar
  32. 32.
    Colombini M., Blachy-Dyson E., Forte M. 1996. VDAC, a channel in the outer membrane. Ion Channels. 4, 169–202.PubMedGoogle Scholar
  33. 33.
    Kmita H., Budzinska M., Stobienia O. 2003. Modulation of the voltage-dependent anionselective channel by cytoplasmic proteins from wild type and the channel depleted cells of Saccharomyces cerevisiae. Acta Biochim. Pol. 50, 415–424.PubMedGoogle Scholar
  34. 34.
    Kmita H., Antos N., Wojtkowska M., Hryniewiecka L. 2004. Processes underlying the upregulation of Tom proteins in S. cerevisiae mitochondria depleted of the VDAC channel. J. Bioenerg. Biomembr. 36, 187–193.PubMedCrossRefGoogle Scholar
  35. 35.
    Poleti M.D., Tesch A.C., Crepaldi C.R., Souza G.H., Eberlin M.N., de Cerqueira C.M. 2010. Relationship between expression of voltage-dependent anion channel (VDAC) isoforms and type of hexokinase binding sites on brain mitochondria. J. Mol. Neurosci. 41, 48–54.PubMedCrossRefGoogle Scholar
  36. 36.
    Yamamoto T., Yamada A., Watanabe M., Yoshimura Y., Yamazaki N., Yoshimura Y., Yamauchi T., Kataoka M., Nagata T., Terada H., Shinohara Y. 2006. VDAC1, having a shorter N-terminus than VDAC2 but showing the same migration in an SDS-polyacrylamide gel, is the predominant form expressed in mitochondria of various tissues. J. Proteome Res. 5, 3336–3344.PubMedCrossRefGoogle Scholar
  37. 37.
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. 2009. Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. 81, 4493–4501.PubMedCrossRefGoogle Scholar
  38. 38.
    Kayser H., Kratzin H.D., Thinnes F.P., Gotz H., Schmidt W.E., Eckart K., Hilschmann N. 1989. Identification of human porins. II. Characterization and primary structure of a 31-lDa porin from human B lymphocytes (Porin 31HL). Biol. Chem. Hoppe Seyler. 370, 1265–1278.PubMedGoogle Scholar
  39. 39.
    Distler A.M., Kerner J., Hoppel C.L. 2007. Posttranslational modifications of rat liver mitochondrial outer membrane proteins identified by mass spectrometry. Biochim. Biophys. Acta. 1774, 628–636.PubMedGoogle Scholar
  40. 40.
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. 2009. Lysine acetylation targets protein complexes and coregulates major cellular functions. Science. 325, 834–840.PubMedCrossRefGoogle Scholar
  41. 41.
    Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. 2008. A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. USA. 105, 10762–10767.PubMedCrossRefGoogle Scholar
  42. 42.
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. 2006. Global, in vivo, and sitespecific phosphorylation dynamics in signaling networks. Cell. 127, 635–648.PubMedCrossRefGoogle Scholar
  43. 43.
    Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schutz C., Walter U., Gambaryan S., Sickmann A. 2008. Phosphoproteome of resting human platelets. J. Proteome Res. 7, 526–534.PubMedCrossRefGoogle Scholar
  44. 44.
    Wang B., Malik R., Nigg E.A., Korner R. 2008. Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal. Chem. 80, 9526–9533.PubMedCrossRefGoogle Scholar
  45. 45.
    Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.M., Polakiewicz R.D., Comb M.J. 2005. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. 23, 94–101.PubMedCrossRefGoogle Scholar
  46. 46.
    Sampson M.J., Lovell R.S., Craigen W.J. 1997. The murine voltage-dependent anion channel gene family. Conserved structure and function. J. Biol. Chem. 272, 18966–18973.PubMedCrossRefGoogle Scholar
  47. 47.
    Xu X., Decker W., Sampson M.J., Craigen W.J., Colombini M. 1999. Mouse VDAC isoforms expressed in yeast: Channel properties and their roles in mitochondrial outer membrane permeability. J. Membr. Biol. 170, 89–102.PubMedCrossRefGoogle Scholar
  48. 48.
    Craigen W.J., Graham B.H. 2008. Genetic strategies for dissecting mammalian and Drosophila voltage-dependent anion channel functions. J. Bioenerg. Biomembr. 40, 207–212.PubMedCrossRefGoogle Scholar
  49. 49.
    Komarov A.G., Deng D., Craigen W.J., Colombini M. 2005. New insights into the mechanism of permeation through large channels. Biophys. J. 89, 3950–3959.PubMedCrossRefGoogle Scholar
  50. 50.
    Blachly-Dyson E., Zambronicz E.B., Yu W.H., Adams V., McCabe E.R., Adelman J., Colombini M., Forte M. 1993. Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel. J. Biol. Chem. 268, 1835–1841.PubMedGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    Wu S., Sampson M.J., Decker W.K., Craigen W.J. 1999. Each mammalian mitochondrial outer membrane porin protein is dispensable: Effects on cellular respiration. Biochim. Biophys. Acta. 1452, 68–78.PubMedCrossRefGoogle Scholar
  53. 53.
    van Ekeren G.J., Stadhouders A.M., Smeitink J.A., Sengers R.C. 1993. A retrospective study of patients with the hereditary syndrome of congenital cataract, mitochondrial myopathy of heart and skeletal muscle and lactic acidosis. Eur. J. Pediatr. 152, 255–259.PubMedCrossRefGoogle Scholar
  54. 54.
    Tsujimoto Y., Shimizu S. 2002. The voltage-dependent anion channel: An essential player in apoptosis. Biochimie. 84, 187–193.PubMedCrossRefGoogle Scholar
  55. 55.
    Zoratti M., Szabo D., De Marchi U. 2005. Mitochondrial permeability transitions: How many doors to the house? Biochim. Biophys. Acta. 1706, 40–52.PubMedCrossRefGoogle Scholar
  56. 56.
    Bernardi P., Krauskopf A., Basso E., Petronilli V., Blachly-Dyson E., Di Lisa F., Forte M.A. 2006. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J. 273, 2077–2099.PubMedCrossRefGoogle Scholar
  57. 57.
    Tan W.Z., Colombini M. 2007. VDAC closure increases calcium ion flux. Biochim. Biophys. Acta. 1768, 2510–2515.PubMedCrossRefGoogle Scholar
  58. 58.
    Tan W.Z., Lai J.C., Miller P., Stein C.A., Colombini M. 2007. Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP. Am. J. Physiol. Cell Physiol. 292, C1388–C1397.PubMedCrossRefGoogle Scholar
  59. 59.
    Cheng E.H., Sheiko T.V., Fisher J.K., Craigen W.J., Korsmeyer S.J. 2003. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science. 301, 513–517.PubMedCrossRefGoogle Scholar
  60. 60.
    Baines C.P., Kaiser R.A., Sheiko T., Craigen W.J., Molkentin J.D. 2007. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat. Cell Biol. 9, 550–555.PubMedCrossRefGoogle Scholar
  61. 61.
    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.PubMedCrossRefGoogle Scholar
  62. 62.
    Shoshan-Barmatz V., Keinan N., Abu-Hamad S., Toymki D., Aram L. 2010. Apoptosis is regulated by the VDAC1 N-terminal region and by VDAC oligomerization: Release of cytochrome c, AIF and Smac/Diablo. Biochim. Biophys. Acta. 1797, 1281–1291.PubMedCrossRefGoogle Scholar
  63. 63.
    Lazarou M., Stojanovski D., Frazier A.E., Kotevski A., Dewson G., Craigen W.J., Kluck R.M., Vaux D.L., Michael T. Ryan M.T. 2010. Inhibition of bak activation by VDAC2 is dependent on the bak transmembrane anchor. J. Biol. Chem. 285, 36876–36883.PubMedCrossRefGoogle Scholar
  64. 64.
    Setoguchi K., Otera H., Mihara K. 2006. Cytosolic factor- and TOM-independent import of C-tail-anchored mitochondrial outer membrane proteins. EMBO J. 25, 5635–5647.PubMedCrossRefGoogle Scholar
  65. 65.
    Yamagata H., Shimizu S., Nishida Y., Watanabe Y., Craigen W.J., Tsujimoto Y. 2009. Requirement of voltage-dependent anion channel 2 for proapoptotic activity of Bax. Oncogene. 28, 3563–3572.PubMedCrossRefGoogle Scholar
  66. 66.
    Anflous K., Armstrong D.D., Craigen W.J. 2001. Altered mitochondrial sensitivity for ADP and maintenance of creatine-stimulated respiration in oxidative striated muscles from VDAC1-deficient mice. J. Biol. Chem. 276, 1954–1960.PubMedCrossRefGoogle Scholar
  67. 67.
    Sampson M.J., Decker W.K., Beaudet A.L., Ruitenbeek W., Armstrong D., Hicks M.J., Craigen W.J. 2001. Immotile sperm and infertility in mice lacking mitochondrial voltage-dependent anion channel type 3. J. Biol. Chem. 276, 39206–39212.PubMedCrossRefGoogle Scholar
  68. 68.
    Lyon M.F. 2003. Transmission ratio distortion in mice. Annu. Rev. Genet. 37, 393–408.PubMedCrossRefGoogle Scholar
  69. 69.
    Lyon M.F. 2005. Elucidating mouse transmission ratio distortion. Nat. Genet. 37, 924–925.PubMedCrossRefGoogle Scholar
  70. 70.
    Weeber E.J., Levy M., Sampson M.J., Anflous K., Armstrong D.L., Brown S.E., Sweatt J.D., Craigen W.J. 2002. The role of mitochondrial porins and the permeability transition pore in learning and synaptic plasticity. J. Biol. Chem. 277, 18891–18897.PubMedCrossRefGoogle Scholar
  71. 71.
    Graham B.H., David S.J., Craigen W.J. 2002. Noninvasive, in vivo approaches to evaluating behavior and exercise physiology in mouse models of mitochondrial disease. Methods. 26, 364–370.PubMedCrossRefGoogle Scholar
  72. 72.
    Anflous-Pharayra K., Cai Z.J., Craigen W.J. 2007. VDAC1 serves as a mitochondrial binding site for hexokinase in oxidative muscles. Biochim. Biophys. Acta. 1767, 136–142.PubMedCrossRefGoogle Scholar
  73. 73.
    Huizing M., Ruitenbeek W., Thinnes F.P., DePinto V. 1994. Lack of voltage-dependent anion channel in human mitochondrial myopathies. Lancet. 344, 762.PubMedCrossRefGoogle Scholar
  74. 74.
    Huizing M., Ruitenbeek W., Thinnes F.P., DePinto V., Wendel U., Trijbels F.J., Smit L.M., ter Laak H.J., van den Heuvel L.P. 1996. Deficiency of the voltage-dependent anion channel: A novel cause of mitochondriopathy. Pediatr. Res. 39, 760–765.PubMedCrossRefGoogle Scholar
  75. 75.
    De Pinto V., Messina A., Schmid A., Simonetti S., Carnevale F., Benz R. 2000. Characterization of channel-forming activity in muscle biopsy from a porin-deficient human patient. J. Bioenerg. Biomembr. 32, 585–593.PubMedCrossRefGoogle Scholar
  76. 76.
    Yoo B.C., Fountoulakis M., Cairns N., Lubec G. 2001. Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer’s and Down syndrome. Electrophoresis. 22, 172–179.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • V. V. Teplova
    • 1
  • I. V. Odinokova
    • 1
  • E. L. Holmuhamedov
    • 1
  1. 1.Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino, Moscow obl.Russia

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