SpringerLink
Log in

Pore-Forming VDAC Proteins of the Outer Mitochondrial Membrane: Regulation and Pathophysiological Role

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Voltage-dependent anion channels (VDAC1-3) of the outer mitochondrial membrane are a family of pore-forming β-barrel proteins that carry out controlled “filtration” of small molecules and ions between the cytoplasm and mitochondria. Due to the conformational transitions between the closed and open states and interaction with cytoplasmic and mitochondrial proteins, VDACs not only regulate the mitochondrial membrane permeability for major metabolites and ions, but also participate in the control of essential intracellular processes and pathological conditions. This review discusses novel data on the molecular structure, regulatory mechanisms, and pathophysiological role of VDAC proteins, as well as future directions in this area of research.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Abbreviations

ALS:

amyotrophic lateral sclerosis

IMM:

inner mitochondrial membrane

mPTP:

mitochondrial permeability transition pore

OMM:

outer mitochondrial membrane

ROS:

reactive oxygen species

SOD1:

superoxide dismutase 1

VDACs:

voltage-dependent anion channels

References

  1. Jenkins, B. C., Neikirk, K., Katti, P., Claypool, S. M., Kirabo, A., McReynolds, M. R., and Hinton, A., Jr. (2024) Mitochondria in disease: changes in shapes and dynamics, Trends Biochem. Sci., 49, 346-360, https://doi.org/10.1016/j.tibs.2024.01.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Spinelli, J. B., and Haigis, M. C. (2018) The multifaceted contributions of mitochondria to cellular metabolism, Nat. Cell Biol., 20, 745-754, https://doi.org/10.1038/s41556-018-0124-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. **a, D., Liu, Y., Wu, P., and Wei, D. (2023) Current advances of mitochondrial dysfunction and cardiovascular disease and promising therapeutic strategies, Am. J. Pathol., 193, 1485-1500, https://doi.org/10.1016/j.ajpath.2023.06.013.

    Article  CAS  PubMed  Google Scholar 

  4. Shoshan-Barmatz, V., Shteinfer-Kuzmine, A., and Verma, A. (2020) VDAC1 at the intersection of cell metabolism, apoptosis, and diseases, Biomolecules, 10, 1485, https://doi.org/10.3390/biom10111485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. De Pinto, V. (2021) Renaissance of VDAC: new insights on a protein family at the interface between mitochondria and cytosol, Biomolecules, 11, 107, https://doi.org/10.3390/biom11010107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lemeshko, V. V. (2023) VDAC as a voltage-dependent mitochondrial gatekeeper under physiological conditions, Biochim. Biophys. Acta Biomembr., 1865, 184175, https://doi.org/10.1016/j.bbamem.2023.184175.

    Article  CAS  PubMed  Google Scholar 

  7. Varughese, J. T., Buchanan, S. K., and Pitt, A. S. (2021) The role of voltage-dependent anion channel in mitochondrial dysfunction and human disease, Cells, 10, 1737, https://doi.org/10.3390/cells10071737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schein, S. J., Colombini, M., and Finkelstein, A. (1976) Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained from paramecium mitochondria, J. Membr. Biol., 30, 99-120, https://doi.org/10.1007/BF01869662.

    Article  CAS  PubMed  Google Scholar 

  9. Fuchs, P., Rugen, N., Carrie, C., Elsässer, M., Finkemeier, I., Giese, J., Hildebrandt, T. M., Kühn, K., Maurino, V. G., Ruberti, C., Schallenberg-Rüdinger, M., Steinbeck, J., Braun, H. P., Eubel, H., Meyer, E. H., Müller-Schüssele, S. J., and Schwarzländer, M. (2020) Single organelle function and organization as estimated from Arabidopsis mitochondrial proteomics, Plant J., 101, 420-441, https://doi.org/10.1111/tpj.14534.

    Article  CAS  PubMed  Google Scholar 

  10. Magrì, A., Reina, S., and De Pinto, V. (2018) VDAC1 as pharmacological target in cancer and neurodegeneration: focus on its role in apoptosis, Front. Chem., 6, 108, https://doi.org/10.3389/fchem.2018.00108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Maldonado, E. N., and Lemasters, J. J. (2012) Warburg revisited: regulation of mitochondrial metabolism by voltage-dependent anion channels in cancer cells, J. Pharmacol. Exp. Ther., 342, 637-641, https://doi.org/10.1124/jpet.112.192153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shoshan-Barmatz, V., Anand, U., Nahon-Crystal, E., Di Carlo, M., and Shteinfer-Kuzmine, A. (2021) Adverse effects of metformin from diabetes to COVID-19, cancer, neurodegenerative diseases, and aging: is VDAC1 a common target? Front. Physiol., 12, 730048, https://doi.org/10.3389/fphys.2021.730048.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Han, W., Du, C., Zhu, Y., Ran, L., Wang, Y., **ong, J., Wu, Y., Lan, Q., Wang, Y., Wang, L., Wang, J., Yang, K., and Zhao, J. (2022) Targeting myocardial mitochondria-STING-polyamine axis prevents cardiac hypertrophy in chronic kidney disease, JACC Basic Transl. Sci., 7, 820-840, https://doi.org/10.1016/j.jacbts.2022.03.006.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sampson, M. J., Lovell, R. S., and Craigen, W. J. (1997) The murine voltage-dependent anion channel gene family. Conserved structure and function, J. Biol. Chem., 272, 18966-18973, https://doi.org/10.1074/jbc.272.30.18966.

    Article  CAS  PubMed  Google Scholar 

  15. Young, M. J., Bay, D. C., Hausner, G., and Court, D. A. (2007) The evolutionary history of mitochondrial porins, BMC Evol. Biol., 7, 31, https://doi.org/10.1186/1471-2148-7-31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Messina, A., Reina, S., Guarino, F., and De Pinto, V. (2012) VDAC isoforms in mammals, Biochim. Biophys. Acta, 1818, 1466-1476, https://doi.org/10.1016/j.bbamem.2011.10.005.

    Article  CAS  PubMed  Google Scholar 

  17. Benz, R. (1994) Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins, Biochim. Biophys. Acta, 1197, 167-196, https://doi.org/10.1016/0304-4157(94)90004-3.

    Article  CAS  PubMed  Google Scholar 

  18. Hodge, T., and Colombini, M. (1997) Regulation of metabolite flux through voltage-gating of VDAC channels, J. Membr. Biol., 157, 271-279, https://doi.org/10.1007/s002329900235.

    Article  CAS  PubMed  Google Scholar 

  19. Rostovtseva, T., and Colombini, M. (1997) VDAC channels mediate and gate the flow of ATP: implications for the regulation of mitochondrial function, Biophys. J., 72, 1954-1962, https://doi.org/10.1016/S0006-3495(97)78841-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Heslop, K. A., Milesi, V., and Maldonado, E. N. (2021) VDAC modulation of cancer metabolism: advances and therapeutic challenges, Front Physiol., 12, 742839, https://doi.org/10.3389/fphys.2021.742839.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mannella, C. A. (2021) VDAC-A primal perspective, Int. J. Mol. Sci., 22, 1685, https://doi.org/10.3390/ijms22041685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jahn, H., Bartoš, L., Dearden, G. I., Dittman, J. S., Holthuis, J. C. M., Vácha, R., and Menon, A. K. (2023) Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase, Nat. Commun., 14, 8115, https://doi.org/10.1038/s41467-023-43570-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bayrhuber, M., Meins, T., Habeck, M., Becker, S., Giller, K., Villinger, S., Vonrhein, C., Griesinger, C., Zweckstetter, M., and Zeth, K. (2008) Structure of the human voltage-dependent anion channel, Proc. Natl. Acad. Sci. USA, 105, 15370-15375, https://doi.org/10.1073/pnas.0808115105.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hiller, S., Garces, R. G., Malia, T. J., Orekhov, V. Y., Colombini, M., and Wagner, G. (2008) Solution structure of the integral human membrane protein VDAC-1 in detergent micelles, Science, 321, 1206-1210, https://doi.org/10.1126/science.1161302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ujwal, R., Cascio, D., Colletier, J. P., Faham, S., Zhang, J., Toro, L., **, P., and 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, https://doi.org/10.1073/pnas.0809634105.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schredelseker, J., Paz, A., López, C. J., Altenbach, C., Leung, C. S., Drexler, M. K., Chen, J. N., Hubbell, W. L., and Abramson, J. (2014) High resolution structure and double electron-electron resonance of the zebrafish voltage-dependent anion channel 2 reveal an oligomeric population, J. Biol. Chem., 289, 12566-12577, https://doi.org/10.1074/jbc.M113.497438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Naghdi, S., and Hajnóczky, G. (2016) VDAC2-specific cellular functions and the underlying structure, Biochim. Biophys. Acta, 1863, 2503-2514, https://doi.org/10.1016/j.bbamcr.2016.04.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang, E., Mohammed Al-Amily, I., Mohammed, S., Luan, C., Asplund, O., Ahmed, M., Ye, Y., Ben-Hail, D., Soni, A., Vishnu, N., Bompada, P., De Marinis, Y., Groop, L., Shoshan-Barmatz, V., Renström, E., Wollheim, C. B., and Salehi, A. (2019) Preserving insulin secretion in diabetes by inhibiting VDAC1 overexpression and surface translocation in β cells, Cell Metab., 29, 64-77.e6, https://doi.org/10.1016/j.cmet.2018.09.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nepal, C., Hadzhiev, Y., Balwierz, P., Tarifeño-Saldivia, E., Cardenas, R., Wragg, J. W., Suzuki, A. M., Carninci, P., Peers, B., Lenhard, B., Andersen, J. B., and Müller, F. (2020) Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing, Nat. Commun., 11, 168, https://doi.org/10.1038/s41467-019-13687-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zinghirino, F., Pappalardo, X. G., Messina, A., Guarino, F., and De Pinto, V. (2020) Is the secret of VDAC Isoforms in their gene regulation? Characterization of human VDAC genes expression profile, promoter activity, and transcriptional regulators, Int. J. Mol. Sci., 21, 7388, https://doi.org/10.3390/ijms21197388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Neumann, D., Bückers, J., Kastrup, L., Hell, S. W., and Jakobs, S. (2010) Two-color STED microscopy reveals different degrees of colocalization between hexokinase-I and the three human VDAC isoforms, PMC Biophys., 3, 4, https://doi.org/10.1186/1757-5036-3-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zinghirino, F., Pappalardo, X. G., Messina, A., Nicosia, G., De Pinto, V., and Guarino, F. (2021) VDAC genes expression and regulation in mammals, Front. Physiol., 12, 708695, https://doi.org/10.3389/fphys.2021.708695.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Shoshan-Barmatz, V., Maldonado, E. N., and Krelin, Y. (2017) VDAC1 at the crossroads of cell metabolism, apoptosis and cell stress, Cell Stress, 1, 11-36, https://doi.org/10.15698/cst2017.10.104.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Rostovtseva, T. K., Bezrukov, S. M., and Hoogerheide, D. P. (2021) Regulation of mitochondrial respiration by VDAC is enhanced by membrane-bound inhibitors with disordered polyanionic C-terminal domains, Int. J. Mol. Sci., 22, 7358, https://doi.org/10.3390/ijms22147358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tan, W., and Colombini, M. (2007) VDAC closure increases calcium ion flux, Biochim. Biophys. Acta, 1768, 2510-2515, https://doi.org/10.1016/j.bbamem.2007.06.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Xu, X., Decker, W., Sampson, M. J., Craigen, W. J., and 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, https://doi.org/10.1007/s002329900540.

    Article  CAS  PubMed  Google Scholar 

  37. Checchetto, V., Reina, S., Magrì, A., Szabo, I., and De Pinto, V. (2014) Recombinant human voltage dependent anion selective channel isoform 3 (hVDAC3) forms pores with a very small conductance, Cell Physiol. Biochem., 34, 842-853, https://doi.org/10.1159/000363047.

    Article  CAS  PubMed  Google Scholar 

  38. Sander, P., Gudermann, T., and Schredelseker, J. (2021) A calcium guard in the outer membrane: is VDAC a regulated gatekeeper of mitochondrial calcium uptake? Int. J. Mol. Sci., 22, 946, https://doi.org/10.3390/ijms22020946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Shuvo, S. R., Ferens, F. G., and Court, D. A. (2016) The N-terminus of VDAC: Structure, mutational analysis, and a potential role in regulating barrel shape, Biochim. Biophys. Acta, 1858, 1350-1361, https://doi.org/10.1016/j.bbamem.2016.03.017.

    Article  CAS  PubMed  Google Scholar 

  40. Lemeshko, V. V. (2021) Electrical control of the cell energy metabolism at the level of mitochondrial outer membrane, Biochim. Biophys. Acta Biomembr., 1863, 183493, https://doi.org/10.1016/j.bbamem.2020.183493.

    Article  CAS  PubMed  Google Scholar 

  41. Roll-Mecak, A. (2015) Intrinsically disordered tubulin tails: complex tuners of microtubule functions? Semin. Cell. Dev. Biol., 37, 11-19, https://doi.org/10.1016/j.semcdb.2014.09.026.

    Article  CAS  PubMed  Google Scholar 

  42. Jiang, Z., Heinrich, F., McGlinchey, R. P., Gruschus, J. M., and Lee, J. C. (2017) Segmental deuteration of α-synuclein for neutron reflectometry on tethered bilayers, J. Phys. Chem. Lett., 8, 29-34, https://doi.org/10.1021/acs.jpclett.6b02304.

    Article  CAS  PubMed  Google Scholar 

  43. Hoogerheide, D. P., Noskov, S. Y., Jacobs, D., Bergdoll, L., Silin, V., Worcester, D. L., Abramson, J., Nanda, H., Rostovtseva, T. K., and Bezrukov, S. M. (2017) Structural features and lipid binding domain of tubulin on biomimetic mitochondrial membranes, Proc. Natl. Acad. Sci. USA, 114, E3622-E3631, https://doi.org/10.1073/pnas.1619806114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rostovtseva, T. K., Gurnev, P. A., Chen, M. Y., and Bezrukov, S. M. (2012) Membrane lipid composition regulates tubulin interaction with mitochondrial voltage-dependent anion channel, J. Biol. Chem., 287, 29589-29598, https://doi.org/10.1074/jbc.M112.378778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rostovtseva, T. K., and Bezrukov, S. M. (2012) VDAC inhibition by tubulin and its physiological implications, Biochim. Biophys. Acta, 1818, 1526-1535, https://doi.org/10.1016/j.bbamem.2011.11.004.

    Article  CAS  PubMed  Google Scholar 

  46. Rostovtseva, T. K., Gurnev, P. A., Protchenko, O., Hoogerheide, D. P., Yap, T. L., Philpott, C. C., Lee, J. C., and Bezrukov, S. M. (2015) α-Synuclein shows high affinity interaction with voltage-dependent anion channel, suggesting mechanisms of mitochondrial regulation and toxicity in Parkinson’s disease, J. Biol. Chem., 290, 18467-18477, https://doi.org/10.1074/jbc.M115.641746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Guzun, R., Gonzalez-Granillo, M., Karu-Varikmaa, M., Grichine, A., Usson, Y., Kaambre, T., Guerrero-Roesch, K., Kuznetsov, A., Schlattner, U., and Saks, V. (2012) Regulation of respiration in muscle cells in vivo by VDAC through interaction with the cytoskeleton and MtCK within mitochondrial interactosome, Biochim. Biophys. Acta, 1818, 1545-1554, https://doi.org/10.1016/j.bbamem.2011.12.034.

    Article  CAS  PubMed  Google Scholar 

  48. Mado, K., Chekulayev, V., Shevchuk, I., Puurand, M., Tepp, K., and Kaambre, T. (2019) On the role of tubulin, plectin, desmin, and vimentin in the regulation of mitochondrial energy fluxes in muscle cells, Am. J. Physiol Cell Physiol., 316, C657-C667, https://doi.org/10.1152/ajpcell.00303.2018.

    Article  CAS  PubMed  Google Scholar 

  49. Dayal, A. A., Medvedeva, N. V., Nekrasova, T. M., Duhalin, S. D., Surin, A. K., Minin, A. A. (2020) Desmin interacts directly with mitochondria, Int. J. Mol. Sci., 21, 8122, https://doi.org/10.3390/ijms21218122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chernoivanenko, I. S., Matveeva, E. A., Gelfand, V. I., Goldman, R. D., and Minin, A. A. (2015) Mitochondrial membrane potential is regulated by vimentin intermediate filaments, FASEB J., 29, 820-827, https://doi.org/10.1096/fj.14-259903.

    Article  CAS  PubMed  Google Scholar 

  51. Mathupala, S. P., Ko, Y. H., and Pedersen, P. L. (2010) The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging prospects for effective therapies, Biochim. Biophys. Acta, 1797, 1225-1230, https://doi.org/10.1016/j.bbabio.2010.03.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mariani, M., Karki, R., Spennato, M., Pandya, D., He, S., Andreoli, M., Fiedler, P., and Ferlini, C. (2015) Class III β-tubulin in normal and cancer tissues, Gene, 563, 109-114, https://doi.org/10.1016/j.gene.2015.03.061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Goedert, M., Jakes, R., and Spillantini, M. G. (2017) The synucleinopathies: twenty years on, J. Parkinsons Dis., 7, S51-S69, https://doi.org/10.3233/JPD-179005.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Reeve, A. K., Ludtmann, M. H., Angelova, P. R., Simcox, E. M., Horrocks, M. H., Klenerman, D., Gandhi, S., Turnbull, D. M., and Abramov, A. Y. (2015) Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons, Cell Death Dis., 6, e1820, https://doi.org/10.1038/cddis.2015.166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ludtmann, M. H. R., Angelova, P. R., Horrocks, M. H., Choi, M. L., Rodrigues, M., Baev, A. Y., Berezhnov, A. V., Yao, Z., Little, D., Banushi, B., Al-Menhali, A. S., Ranasinghe, R. T., Whiten, D. R., Yapom, R., Dolt, K. S., Devine, M. J., Gissen, P., Kunath, T., Jaganjac, M., Pavlov, E. V., Klenerman, D., Abramov, A. Y., and Gandhi, S. (2018) α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease, Nat. Commun., 9, 2293, https://doi.org/10.1038/s41467-018-04422-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pastorino, J. G., Shulga, N., and Hoek, J. B. (2002) Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis, J. Biol. Chem., 277, 7610-7618, https://doi.org/10.1074/jbc.M109950200.

    Article  CAS  PubMed  Google Scholar 

  57. 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: map** the site of binding, J. Biol. Chem., 283, 13482-13490, https://doi.org/10.1074/jbc.M708216200.

    Article  CAS  PubMed  Google Scholar 

  58. Azoulay-Zohar, H., Israelson, A., Abu-Hamad, S., and 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, https://doi.org/10.1042/BJ20031465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Arbel, N., Ben-Hail, D., and Shoshan-Barmatz, V. (2012) Mediation of the antiapoptotic activity of Bcl-xL protein upon interaction with VDAC1 protein, J. Biol. Chem., 287, 23152-23161, https://doi.org/10.1074/jbc.M112.345918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Krasnov, G. S., Dmitriev, A. A., Lakunina, V. A., Kirpiy, A. A., and Kudryavtseva, A. V. (2013) Targeting VDAC-bound hexokinase II: a promising approach for concomitant anti-cancer therapy, Expert Opin. Ther. Targets, 17, 1221-1233, https://doi.org/10.1517/14728222.2013.833607.

    Article  CAS  PubMed  Google Scholar 

  61. Al Jamal, J. A. (2005) Involvement of porin N,N-dicyclohexylcarbodiimide-reactive domain in hexokinase binding to the outer mitochondrial membrane, Protein J., 24, 1-8, https://doi.org/10.1007/s10930-004-0600-2.

    Article  CAS  PubMed  Google Scholar 

  62. Juhaszova, M., Wang, S., Zorov, D. B., Nuss, H. B., Gleichmann, M., Mattson, M. P., and Sollott, S. J. (2008) The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown, Ann. N. Y. Acad. Sci., 1123, 197-212, https://doi.org/10.1196/annals.1420.023.

    Article  CAS  PubMed  Google Scholar 

  63. Halestrap, A. P., and Richardson, A. P. (2015) The mitochondrial permeability transition: a current perspective on its identity and role in ischaemia/reperfusion injury, J. Mol. Cell. Cardiol., 78, 129-141, https://doi.org/10.1016/j.yjmcc.2014.08.018.

    Article  CAS  PubMed  Google Scholar 

  64. Guo, D., Meng, Y., Jiang, X., and Lu, Z. (2023) Hexokinases in cancer and other pathologies, Cell Insight., 2, 100077, https://doi.org/10.1016/j.cellin.2023.100077.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zaid, H., Abu-Hamad, S., Israelson, A., Nathan, I., and Shoshan-Barmatz, V. (2005) The voltage-dependent anion channel-1 modulates apoptotic cell death, Cell Death Differ., 12, 751-760, https://doi.org/10.1038/sj.cdd.4401599.

    Article  CAS  PubMed  Google Scholar 

  66. Rister, A. B., Gudermann, T., Schredelseker, J. (2022) E as in enigma: the mysterious role of the voltage-dependent anion channel glutamate E73, Int. J. Mol. Sci., 24, 269, https://doi.org/10.3390/ijms24010269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nakashima, R. A. (1989) Hexokinase-binding properties of the mitochondrial VDAC protein: inhibition by DCCD and location of putative DCCD-binding sites, J. Bioenerg. Biomembr., 21, 461-470, https://doi.org/10.1007/BF00762518.

    Article  CAS  PubMed  Google Scholar 

  68. Dolder, M., Wendt, S., and Wallimann, T. (2001) Mitochondrial creatine kinase in contact sites: interaction with porin and adenine nucleotide translocase, role in permeability transition and sensitivity to oxidative damage, Biol. Signals Recept., 10, 93-111, https://doi.org/10.1159/000046878.

    Article  CAS  PubMed  Google Scholar 

  69. Gliozzi, M., Scarano, F., Musolino, V., Carresi, C., Scicchitano, M., Ruga, S., Zito, M. C., Nucera, S., Bosco, F., Maiuolo, J., Macrì, R., Guarnieri, L., Mollace, R., Coppoletta, A. R., Nicita, C., Tavernese, A., Palma, E., Muscoli, C., and Mollace, V. (2020) Role of TSPO/VDAC1 upregulation and matrix metalloproteinase-2 localization in the dysfunctional myocardium of hyperglycaemic rats, Int. J. Mol. Sci., 21, 7432, https://doi.org/10.3390/ijms21207432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wolff, S., Erster, S., Palacios, G., and Moll, U. M. (2008) p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity, Cell Res., 18, 733-744, https://doi.org/10.1038/cr.2008.62.

    Article  CAS  PubMed  Google Scholar 

  71. Sasaki, S., Yui, N., and Noda, Y. (2014) Actin directly interacts with different membrane channel proteins and influences channel activities: AQP2 as a model, Biochim. Biophys. Acta, 1838, 514-520, https://doi.org/10.1016/j.bbamem.2013.06.004.

    Article  CAS  PubMed  Google Scholar 

  72. Pittalà, M. G. G., Conti Nibali, S., Reina, S., Cunsolo, V., Di Francesco, A., De Pinto, V., Messina, A., Foti, S., and Saletti, R. (2021) VDACs post-translational modifications discovery by mass spectrometry: impact on their hub function, Int. J. Mol. Sci., 22, 12833, https://doi.org/10.3390/ijms222312833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Najbauer, E. E., Becker, S., Giller, K., Zweckstetter, M., Lange, A., Steinem, C., de Groot, B. L., Griesinger, C., and Andreas, L. B. (2021) Structure, gating and interactions of the voltage-dependent anion channel, Eur. Biophys. J., 50, 159-172, https://doi.org/10.1007/s00249-021-01515-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Reina, S., and Checchetto, V. (2022) Voltage-dependent anion selective channel 3: unraveling structural and functional features of the least known porin isoform, Front. Physiol., 12, 784867, https://doi.org/10.3389/fphys.2021.784867.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Bergdoll, L. A., Lerch, M. T., Patrick, J. W., Belardo, K., Altenbach, C., Bisignano, P., Laganowsky, A., Grabe, M., Hubbell, W. L., and Abramson, J. (2018) Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1, Proc. Natl. Acad. Sci. USA, 115, E172-E179, https://doi.org/10.1073/pnas.1715464115.

    Article  CAS  PubMed  Google Scholar 

  76. Keinan, N., Tyomkin, D., and Shoshan-Barmatz, V. (2010) Oligomerization of the mitochondrial protein voltage-dependent anion channel is coupled to the induction of apoptosis, Mol. Cell Biol., 30, 5698-5709, https://doi.org/10.1128/MCB.00165-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shoshan-Barmatz, V., Mizrachi, D., and Keinan, N. (2013) Oligomerization of the mitochondrial protein VDAC1: from structure to function and cancer therapy, Prog. Mol. Biol. Transl. Sci., 117, 303-334, https://doi.org/10.1016/B978-0-12-386931-9.00011-8.

    Article  CAS  PubMed  Google Scholar 

  78. Czabotar, P. E., and Garcia-Saez, A. J. (2023) Mechanisms of BCL-2 family proteins in mitochondrial apoptosis, Nat. Rev. Mol. Cell Biol., 24, 732-748, https://doi.org/10.1038/s41580-023-00629-4.

    Article  CAS  PubMed  Google Scholar 

  79. Vyssokikh, M. Y., Zorova, L., Zorov, D., Heimlich, G., Jürgensmeier, J. J., and Brdiczka, D. (2002) Bax releases cytochrome c preferentially from a complex between porin and adenine nucleotide translocator. Hexokinase activity suppresses this effect, Mol. Biol. Rep., 29, 93-96, https://doi.org/10.1023/A:1020383108620.

    Article  CAS  PubMed  Google Scholar 

  80. Yan, J., Liu, W., Feng, F., and Chen, L. (2020) VDAC oligomer pores: A mechanism in disease triggered by mtDNA release, Cell Biol. Int., 44, 2178-2181, https://doi.org/10.1002/cbin.11427.

    Article  CAS  PubMed  Google Scholar 

  81. Cheng, E. H., Sheiko, T. V., Fisher, J. K., Craigen, W. J., and Korsmeyer, S. J. (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis, Science, 301, 513-517, https://doi.org/10.1126/science.1083995.

    Article  CAS  PubMed  Google Scholar 

  82. Naghdi, S., Várnai, P., and Hajnóczky, G. (2015) Motifs of VDAC2 required for mitochondrial Bak import and tBid-induced apoptosis, Proc. Natl. Acad. Sci. USA, 112, E5590-E5599, https://doi.org/10.1073/pnas.1510574112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chin, H. S., Li, M. X., Tan, I. K. L., Ninnis, R. L., Reljic, B., Scicluna, K., Dagley, L. F., Sandow, J. J., Kelly, G. L., Samson, A. L., Chappaz, S., Khaw, S. L., Chang, C., Morokoff, A., Brinkmann, K., Webb, A., Hockings, C., Hall, C. M., Kueh, A. J., Ryan, M. T., Kluck, R. M., Bouillet, P., Herold, M. J., Gray, D. H. D., Huang, D. C. S., van Delft, M. F., and Dewson, G. (2018) VDAC2 enables BAX to mediate apoptosis and limit tumor development, Nat. Commun., 9, 4976, https://doi.org/10.1038/s41467-018-07309-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Huckabee, D. B., and Jekabsons, M. B. (2011) Identification of Bax-voltage-dependent anion channel 1 complexes in digitonin-solubilized cerebellar granule neurons, J. Neurochem., 119, 1137-1150, https://doi.org/10.1111/j.1471-4159.2011.07499.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Gincel, D., Zaid, H., and Shoshan-Barmatz, V. (2001) Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function, Biochem. J., 358, 147-155, https://doi.org/10.1042/0264-6021:3580147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Belosludtsev, K. N., Dubinin, M. V., Belosludtseva, N. V., and Mironova, G. D. (2019) Mitochondrial Ca2+ transport: mechanisms, molecular structures, and role in cells, Biochemistry (Moscow), 84, 593-607, https://doi.org/10.1134/S0006297919060026.

    Article  CAS  PubMed  Google Scholar 

  87. Lu, B., Chen, X., Ma, Y., Gui, M., Yao, L., Li, J., Wang, M., Zhou, X., and Fu, D. (2024) So close, yet so far away: the relationship between MAM and cardiac disease, Front. Cardiovasc. Med., 11, 1353533, https://doi.org/10.3389/fcvm.2024.1353533.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Van Vliet, A. R., Verfaillie, T., and Agostinis, P. (2014) New functions of mitochondria associated membranes in cellular signaling, Biochim. Biophys. Acta, 1843, 2253-2262, https://doi.org/10.1016/j.bbamcr.2014.03.009.

    Article  CAS  PubMed  Google Scholar 

  89. Giorgi, C., Missiroli, S., Patergnani, S., Duszynski, J., Wieckowski, M. R., and Pinton, P. (2015) Mitochondria-associated membranes: composition, molecular mechanisms, and physiopathological implications, Antioxid. Redox Signal., 22, 995-1019, https://doi.org/10.1089/ars.2014.6223.

    Article  CAS  PubMed  Google Scholar 

  90. Poston, C. N., Krishnan, S. C., and Bazemore-Walker, C. R. (2013) In depth proteomic analysis of mammalian mitochondria-associated membranes (MAM), J. Proteomics, 79, 219-230, https://doi.org/10.1016/j.jprot.2012.12.018.

    Article  CAS  PubMed  Google Scholar 

  91. Dubinin, M. V., Mikheeva, I. B., Stepanova, A. E., Igoshkina, A. D., Cherepanova, A. A., Semenova, A. A., Sharapov, V. A., Kireev, I. I., and Belosludtsev, K. N. (2024) Mitochondrial transplantation therapy ameliorates muscular dystrophy in mdx mouse model, Biomolecules, 14, 316, https://doi.org/10.3390/biom14030316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Rosencrans, W. M., Rajendran, M., Bezrukov, S. M., and Rostovtseva, T. K. (2021) VDAC regulation of mitochondrial calcium flux: from channel biophysics to disease, Cell Calcium, 94, 102356, https://doi.org/10.1016/j.ceca.2021.102356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Harada, T., Sada, R., Osugi, Y., Matsumoto, S., Matsuda, T., Hayashi-Nishino, M., Nagai, T., Harada, A., and Kikuchi, A. (2020) Palmitoylated CKAP4 regulates mitochondrial functions through an interaction with VDAC2 at ER-mitochondria contact sites, J. Cell Sci., 133, jcs249045, https://doi.org/10.1242/jcs.249045.

    Article  CAS  PubMed  Google Scholar 

  94. Min, C. K., Yeom, D. R., Lee, K. E., Kwon, H. K., Kang, M., Kim, Y. S., Park, Z. Y., Jeon, H., and Kim, D. H. (2012) Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is essential for Ca2+ transfer from the sarcoplasmic reticulum to the mitochondria in the heart, Biochem. J., 447, 371-379, https://doi.org/10.1042/BJ20120705.

    Article  CAS  PubMed  Google Scholar 

  95. Liao, Y., Hao, Y., Chen, H., He, Q., Yuan, Z., and Cheng, J. (2015) Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death, Protein Cell, 6, 434-442, https://doi.org/10.1007/s13238-015-0144-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Carraro, M., and Bernardi, P. (2023) The mitochondrial permeability transition pore in Ca2+ homeostasis, Cell Calcium, 111, 102719, https://doi.org/10.1016/j.ceca.2023.102719.

    Article  CAS  PubMed  Google Scholar 

  97. Bernardi, P., Gerle, C., Halestrap, A. P., Jonas, E. A., Karch, J., Mnatsakanyan, N., Pavlov, E., Sheu, S. S., and Soukas, A. A. (2023) Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions, Cell Death Differ., 30, 1869-1885, https://doi.org/10.1038/s41418-023-01187-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Fang, D., and Maldonado, E. N. (2018) VDAC regulation: a mitochondrial target to stop cell proliferation, Adv. Cancer Res., 138, 41-69, https://doi.org/10.1016/bs.acr.2018.02.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Yagoda, N., von Rechenberg, M., Zaganjor, E., Bauer, A. J., Yang, W. S., Fridman, D. J., Wolpaw, A. J., Smukste, I., Peltier, J. M., Boniface, J. J., Smith, R., Lessnick, S. L., Sahasrabudhe, S., and Stockwell, B. R. (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels, Nature, 447, 864-868, https://doi.org/10.1038/nature05859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Maldonado, E. N., Sheldon, K. L., DeHart, D. N., Patnaik, J., Manevich, Y., Townsend, D. M., Bezrukov, S. M., Rostovtseva, T. K., and Lemasters, J. J. (2013) Voltage-dependent anion channels modulate mitochondrial metabolism in cancer cells: regulation by free tubulin and erastin, J. Biol. Chem., 288, 11920-11929, https://doi.org/10.1074/jbc.M112.433847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Heslop, K. A., Rovini, A., Hunt, E. G., Fang, D., Morris, M. E., Christie, C. F., Gooz, M. B., DeHart, D. N., Dang, Y., Lemasters, J. J., and Maldonado, E. N. (2020) JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells, Biochem. Pharmacol., 171, 113728, https://doi.org/10.1016/j.bcp.2019.113728.

    Article  CAS  PubMed  Google Scholar 

  102. Zhao, Y., Li, Y., Zhang, R., Wang, F., Wang, T., and Jiao, Y. (2020) The role of erastin in ferroptosis and its prospects in cancer therapy, Onco Targets Ther., 13, 5429-5441, https://doi.org/10.2147/OTT.S254995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Anghileri, L. J. (1975) The in vivo inhibition of tumor growth by rutheniumred: its relationship with the metabolism of calcium in the tumor, Z. Krebsforsch Klin. Onkol. Cancer Res. Clin. Oncol., 83, 213-217, https://doi.org/10.1007/BF00304090.

    Article  CAS  PubMed  Google Scholar 

  104. Israelson, A., Zaid, H., Abu-Hamad, S., Nahon, E., and Shoshan-Barmatz, V. (2008) Map** the ruthenium red-binding site of the voltage-dependent anion channel-1, Cell Calcium, 43, 196-204, https://doi.org/10.1016/j.ceca.2007.05.006.

    Article  CAS  PubMed  Google Scholar 

  105. Ben-Hail, D., Begas-Shvartz, R., Shalev, M., Shteinfer-Kuzmine, A., Gruzman, A., Reina, S., De Pinto, V., and Shoshan-Barmatz, V. (2016) Novel compounds targeting the mitochondrial protein VDAC1 inhibit apoptosis and protect against mitochondrial dysfunction, J. Biol. Chem., 291, 24986-25003, https://doi.org/10.1074/jbc.M116.744284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Verma, A., Shteinfer-Kuzmine, A., Kamenetsky, N., Pittala, S., Paul, A., Nahon Crystal, E., Ouro, A., Chalifa-Caspi, V., Pandey, S. K., Monsonego, A., Vardi, N., Knafo, S., and Shoshan-Barmatz, V. (2022) Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer’s disease protects against mitochondrial dysfunction and mitigates brain pathology, Transl. Neurodegener., 11, 58, https://doi.org/10.1186/s40035-022-00329-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Belosludtsev, K. N., Ilzorkina, A. I., Matveeva, L. A., Chulkov, A. V., Semenova, A. A., Dubinin, M. V., and Belosludtseva, N. V. (2024) Effect of VBIT-4 on the functional activity of isolated mitochondria and cell viability, Biochim. Biophys. Acta Biomembr., 1866, 184329, https://doi.org/10.1016/j.bbamem.2024.184329.

    Article  CAS  PubMed  Google Scholar 

  108. Nagakannan, P., Islam, M. I., Karimi-Abdolrezaee, S., and Eftekharpour, E. (2019) Inhibition of VDAC1 protects against glutamate-induced oxytosis and mitochondrial fragmentation in hippocampal HT22 cells, Cell. Mol. Neurobiol., 39, 73-85, https://doi.org/10.1007/s10571-018-0634-1.

    Article  CAS  PubMed  Google Scholar 

  109. Zakyrjanova, G. F., Gilmutdinov, A. I., Tsentsevitsky, A. N., and Petrov, A. M. (2020) Olesoxime, a cholesterol-like neuroprotectant restrains synaptic vesicle exocytosis in the mice motor nerve terminals: possible role of VDACs, Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1865, 158739, https://doi.org/10.1016/j.bbalip.2020.158739.

    Article  CAS  PubMed  Google Scholar 

  110. Bordet, T., Berna, P., Abitbol, J. L., and Pruss, R. M. (2010) Olesoxime (TRO19622): A novel mitochondrial-targeted neuroprotective compound, Pharmaceuticals (Basel), 3, 345-368, https://doi.org/10.3390/ph3020345.

    Article  CAS  PubMed  Google Scholar 

  111. Tewari, D., Majumdar, D., Vallabhaneni, S., and Bera, A. K. (2017) Aspirin induces cell death by directly modulating mitochondrial voltage-dependent anion channel (VDAC), Sci. Rep., 7, 45184, https://doi.org/10.1038/srep45184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Penso, J., and Beitner, R. (1998) Clotrimazole and bifonazole detach hexokinase from mitochondria of melanoma cells, Eur. J. Pharmacol., 342, 113-117, https://doi.org/10.1016/S0014-2999(97)01507-0.

    Article  CAS  PubMed  Google Scholar 

  113. Goldin, N., Arzoine, L., Heyfets, A., Israelson, A., Zaslavsky, Z., Bravman, T., Bronner, V., Notcovich, A., Shoshan-Barmatz, V., and Flescher, E. (2008) Methyl jasmonate binds to and detaches mitochondria-bound hexokinase, Oncogene, 27, 4636-4643, https://doi.org/10.1038/onc.2008.108.

    Article  CAS  PubMed  Google Scholar 

  114. Holmuhamedov, E., and Lemasters, J. J. (2009) Ethanol exposure decreases mitochondrial outer membrane permeability in cultured rat hepatocytes, Arch. Biochem. Biophys., 481, 226-233, https://doi.org/10.1016/j.abb.2008.10.036.

    Article  CAS  PubMed  Google Scholar 

  115. Teplova, V. V., Belosludtsev, K. N., Belosludtseva, N. V., and Kholmukhamedov, E. L. (2010) Mitochondria and hepatotoxicity of ethanol [in Russian], Biofizika, 55, 1038-1047.

    CAS  PubMed  Google Scholar 

  116. Lemasters, J. J., Holmuhamedov, E. L., Czerny, C., Zhong, Z., and Maldonado, E. N. (2012) Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect, Biochim. Biophys. Acta, 1818, 1536-1544, https://doi.org/10.1016/j.bbamem.2011.11.034.

    Article  CAS  PubMed  Google Scholar 

  117. Tan, W., Loke, Y. H., Stein, C. A., Miller, P., and Colombini, M. (2007) Phosphorothioate oligonucleotides block the VDAC channel, Biophys. J., 93, 1184-1191, https://doi.org/10.1529/biophysj.107.105379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Lai, J. C., Tan, W., Benimetskaya, L., Miller, P., Colombini, M., and Stein, C. A. (2006) A pharmacologic target of G3139 in melanoma cells may be the mitochondrial VDAC, Proc. Natl. Acad. Sci. USA, 103, 7494-7499, https://doi.org/10.1073/pnas.0602217103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Mannella, C. A., and Guo, X. W. (1990) Interaction between the VDAC channel and a polyanionic effector. An electron microscopic study, Biophys. J., 57, 23-31, https://doi.org/10.1016/S0006-3495(90)82503-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Heslop, K. A., Burger, P., Kappler, C., Solanki, A. K., Gooz, M., Peterson, Y. K., Mills, C., Benton, T., Duncan, S. A., Woster, P. M., and Maldonado, E. N. (2022) Small molecules targeting the NADH-binding pocket of VDAC modulate mitochondrial metabolism in hepatocarcinoma cells, Biomed. Pharmacother., 150, 112928, https://doi.org/10.1016/j.biopha.2022.112928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Jóźwiak, P., Ciesielski, P., Forma, E., Kozal, K., Wójcik-Krowiranda, K., Cwonda, Ł., Bieńkiewicz, A., Bryś, M., and Krześlak, A. (2020) Expression of voltage-dependent anion channels in endometrial cancer and its potential prognostic significance, Tumour Biol., 42, 1010428320951057, https://doi.org/10.1177/1010428320951057.

    Article  CAS  PubMed  Google Scholar 

  122. Wersäll, O. C., Löfstedt, L., Govorov, I., Mints, M., Gabrielson, M., and Shoshan, M. (2021) PGC1α and VDAC1 expression in endometrial cancer, Mol. Clin. Oncol., 14, 42, https://doi.org/10.3892/mco.2020.2203.

    Article  CAS  PubMed  Google Scholar 

  123. Yang, G., Zhou, D., Li, J., Wang, W., Zhong, W., Fan, W., Yu, M., and Cheng, H. (2019) VDAC1 is regulated by BRD4 and contributes to JQ1 resistance in breast cancer, Oncol. Lett., 18, 2340-2347, https://doi.org/10.3892/ol.2019.10534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Vyssokikh, M. Y., and Brdiczka, D. (2003) The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis, Acta Biochim. Pol., 50, 389-404.

    Article  CAS  PubMed  Google Scholar 

  125. Fang, Y., Liu, J., Zhang, Q., She, C., Zheng, R., Zhang, R., Chen, Z., Chen, C., and Wu, J. (2022) Overexpressed VDAC1 in breast cancer as a novel prognostic biomarker and correlates with immune infiltrates, World J. Surg. Oncol., 20, 211, https://doi.org/10.1186/s12957-022-02667-2.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Seo, J. H., Chae, Y. C., Kossenkov, A. V., Lee, Y. G., Tang, H. Y., Agarwal, E., Gabrilovich, D. I., Languino, L. R., Speicher, D. W., Shastrula, P. K., Storaci, A. M., Ferrero, S., Gaudioso, G., Caroli, M., Tosi, D., Giroda, M., Vaira, V., Rebecca, V. W., Herlyn, M., **ao, M., Fingerman, D., Martorella, A., Skordalakes, E., and Altieri, D. C. (2019) MFF regulation of mitochondrial cell death is a therapeutic target in cancer, Cancer Res., 79, 6215-6226, https://doi.org/10.1158/0008-5472.CAN-19-1982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Wang, F., Qiang, Y., Zhu, L., Jiang, Y., Wang, Y., Shao, X., Yin, L., Chen, J., and Chen, Z. (2016) MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis, Tumour Biol., 37, 10235-10246, https://doi.org/10.1007/s13277-016-4836-1.

    Article  CAS  PubMed  Google Scholar 

  128. Zhang, G., Jiang, G., Wang, C., Zhong, K., Zhang, J., Xue, Q., Li, X., **, H., and Li, B. (2016) Decreased expression of microRNA-320a promotes proliferation and invasion of non-small cell lung cancer cells by increasing VDAC1 expression, Oncotarget, 7, 49470-49480, https://doi.org/10.18632/oncotarget.9943.

    Article  PubMed  PubMed Central  Google Scholar 

  129. DeHart, D. N., Lemasters, J. J., and Maldonado, E. N. (2018) Erastin-like anti-warburg agents prevent mitochondrial depolarization induced by free tubulin and decrease lactate formation in cancer cells, SLAS Discov., 23, 23-33, https://doi.org/10.1177/2472555217731556.

    Article  CAS  PubMed  Google Scholar 

  130. DeHart, D. N., Fang, D., Heslop, K., Li, L., Lemasters, J. J., and Maldonado, E. N. (2018) Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells, Biochem. Pharmacol., 148, 155-162, https://doi.org/10.1016/j.bcp.2017.12.022.

    Article  CAS  PubMed  Google Scholar 

  131. Böhm, R., Amodeo, G. F., Murlidaran, S., Chavali, S., Wagner, G., Winterhalter, M., Brannigan, G., and Hiller, S. (2020) The structural basis for low conductance in the membrane protein VDAC upon β-NADH binding and voltage gating, Structure, 28, 206-214.e4, https://doi.org/10.1016/j.str.2019.11.015.

    Article  CAS  PubMed  Google Scholar 

  132. Manczak, M., and Reddy, P. H. (2012) Abnormal interaction of VDAC1 with amyloid beta and phosphorylated tau causes mitochondrial dysfunction in Alzheimer’s disease, Hum. Mol. Genet., 21, 5131-5146, https://doi.org/10.1093/hmg/dds360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Smilansky, A., Dangoor, L., Nakdimon, I., Ben-Hail, D., Mizrachi, D., and Shoshan-Barmatz, V. (2015) The voltage-dependent anion channel 1 mediates amyloid β toxicity and represents a potential target for Alzheimer’s disease therapy, J. Biol. Chem., 290, 30670-30683, https://doi.org/10.1074/jbc.M115.691493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Magri, A., and Messina, A. (2017) Interactions of VDAC with proteins involved in neurodegenerative aggregation: an opportunity for advancement on therapeutic molecules, Curr. Med. Chem., 24, 4470-4487, https://doi.org/10.2174/0929867324666170601073920.

    Article  CAS  PubMed  Google Scholar 

  135. Manczak, M., Sheiko, T., Craigen, W. J., and Reddy, P. H. (2013) Reduced VDAC1 protects against Alzheimer’s disease, mitochondria, and synaptic deficiencies, J. Alzheimers Dis., 37, 679-690, https://doi.org/10.3233/JAD-130761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Shteinfer-Kuzmine, A., Argueti, S., Gupta, R., Shvil, N., Abu-Hamad, S., Gropper, Y., Hoeber, J., Magrì, A., Messina, A., Kozlova, E. N., Shoshan-Barmatz, V., and Israelson, A. (2019) A VDAC1-derived N-terminal peptide inhibits mutant SOD1-VDAC1 interactions and toxicity in the SOD1 model of ALS, Front. Cell Neurosci., 13, 346, https://doi.org/10.3389/fncel.2019.00346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Belosludtseva, N. V., Matveeva, L. A., Belosludtsev, K. N. (2023) Mitochondrial dyshomeostasis as an early hallmark and a therapeutic target in amyotrophic lateral sclerosis, Int. J. Mol. Sci., 24, 16833, https://doi.org/10.3390/ijms242316833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Israelson, A., Arbel, N., Da Cruz, S., Ilieva, H., Yamanaka, K., Shoshan-Barmatz, V., Cleveland, D. W. (2010) Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS, Neuron, 67, 575-587, https://doi.org/10.1016/j.neuron.2010.07.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Sunyach, C., Michaud, M., Arnoux, T., Bernard-Marissal, N., Aebischer, J., Latyszenok, V., Gouarné, C., Raoul, C., Pruss, R. M., Bordet, T., and Pettmann, B. (2012) Olesoxime delays muscle denervation, astrogliosis, microglial activation and motoneuron death in an ALS mouse model, Neuropharmacology, 62, 2346-2352, https://doi.org/10.1016/j.neuropharm.2012.02.013.

    Article  CAS  PubMed  Google Scholar 

  140. Lenglet, T., Lacomblez, L., Abitbol, J. L., Ludolph, A., Mora, J. S., Robberecht, W., Shaw, P. J., Pruss, R. M., Cuvier, V., and Meininger, V. (2014) Mitotarget study group. A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis, Eur. J. Neurol., 21, 529-536, https://doi.org/10.1111/ene.12344.

    Article  CAS  PubMed  Google Scholar 

  141. Abramov, A. Y., Berezhnov, A. V., Fedotova, E. I., Zinchenko, V. P., and Dolgacheva, L. P. (2017) Interaction of misfolded proteins and mitochondria in neurodegenerative disorders, Biochem. Soc. Trans., 45, 1025-1033, https://doi.org/10.1042/BST20170024.

    Article  CAS  PubMed  Google Scholar 

  142. Martínez, J. H., Fuentes, F., Vanasco, V., Alvarez, S., Alaimo, A., Cassina, A., Coluccio Leskow, F., and Velazquez, F. (2018) Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment, Arch Biochem Biophys., 651, 1-12, https://doi.org/10.1016/j.abb.2018.04.018.

    Article  CAS  PubMed  Google Scholar 

  143. Chu, Y., Goldman, J. G., Kelly, L., He, Y., Waliczek, T., and Kordower, J. H. (2014) Abnormal alpha-synuclein reduces nigral voltage-dependent anion channel 1 in sporadic and experimental Parkinson’s disease, Neurobiol. Dis., 69, 1-14, https://doi.org/10.1016/j.nbd.2014.05.003.

    Article  CAS  PubMed  Google Scholar 

  144. Sasaki, K., Donthamsetty, R., Heldak, M., Cho, Y. E., Scott, B. T., and Makino, A. (2012) VDAC: Old protein with new roles in diabetes, Am. J. Physiol. Cell Physiol., 303, C1055-C1060, https://doi.org/10.1152/ajpcell.00087.2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ahmed, M., Muhammed, S. J., Kessler, B., and Salehi, A. (2010) Mitochondrial proteome analysis reveals altered expression of voltage dependent anion channels in pancreatic β-cells exposed to high glucose, Islets, 2, 283-292, https://doi.org/10.4161/isl.2.5.12639.

    Article  PubMed  Google Scholar 

  146. Gong, D., Chen, X., Middleditch, M., Huang, L., Vazhoor Amarsingh, G., Reddy, S., Lu, J., Zhang, S., Ruggiero, K., Phillips, A. R., and Cooper, G. J. (2009) Quantitative proteomic profiling identifies new renal targets of copper(II)-selective chelation in the reversal of diabetic nephropathy in rats, Proteomics, 9, 4309-4320, https://doi.org/10.1002/pmic.200900285.

    Article  CAS  PubMed  Google Scholar 

  147. Lumini-Oliveira, J., Magalhães, J., Pereira, C. V., Moreira, A. C., Oliveira, P. J., and Ascensão, A. (2011) Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia, Mitochondrion, 11, 54-63, https://doi.org/10.1016/j.mito.2010.07.005.

    Article  CAS  PubMed  Google Scholar 

  148. Belosludtsev, K. N., Serov, D. A., Ilzorkina, A. I., Starinets, V. S., Dubinin, M. V., Talanov, E. Y., Karagyaur, M. N., Primak, A. L., and Belosludtseva, N. V. (2023) Pharmacological and genetic suppression of VDAC1 alleviates the development of mitochondrial dysfunction in endothelial and fibroblast cell cultures upon hyperglycemic conditions, Antioxidants, 12, 1459, https://doi.org/10.3390/antiox12071459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Greyslak, K. T., Hetrick, B., Bergman, B. C., Dean, T. A., Wesolowski, S. R., Gannon, M., Schenk, S., Sullivan, E. L., Aagaard, K. M., Kievit, P., Chicco, A. J., Friedman, J. E., and McCurdy, C. E. (2023) A maternal western-style diet impairs skeletal muscle lipid metabolism in adolescent Japanese macaques, Diabetes, 72, 1766-1780, https://doi.org/10.2337/db23-0289.

    Article  CAS  PubMed  Google Scholar 

  150. Rahmani, Z., Huh, K. W., Lasher, R., and Siddiqui, A. (2000) Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential, J. Virol., 74, 2840-2846, https://doi.org/10.1128/jvi.74.6.2840-2846.2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Moin, S. M., Panteva, M., and Jameel, S. (2007) The hepatitis E virus Orf3 protein protects cells from mitochondrial depolarization and death, J. Biol. Chem., 282, 21124-21133, https://doi.org/10.1074/jbc.M701696200.

    Article  CAS  PubMed  Google Scholar 

  152. Qiao, H., and McMillan, J. R. (2007) Gelsolin segment 5 inhibits HIV-induced T-cell apoptosis via Vpr-binding to VDAC, FEBS Lett., 581, 535-540, https://doi.org/10.1016/j.febslet.2006.12.057.

    Article  CAS  PubMed  Google Scholar 

  153. Zamarin, D., García-Sastre, A., **ao, X., Wang, R., and Palese, P. (2005) Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1, PLoS Pathog., 1, e4, https://doi.org/10.1371/journal.ppat.0010004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Jitobaom, K., Tongluan, N., and Smith, D. R. (2016) Involvement of voltage-dependent anion channel (VDAC) in dengue infection, Sci. Rep., 6, 35753, https://doi.org/10.1038/srep35753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Han, C., Zeng, X., Yao, S., Gao, L., Zhang, L., Qi, X., Duan, Y., Yang, B., Gao, Y., Liu, C., Zhang, Y., Wang, Y., and Wang, X. (2017) Voltage-dependent anion channel 1 interacts with ribonucleoprotein complexes to enhance infectious bursal disease virus polymerase activity, J. Virol., 91, e00584-17, https://doi.org/10.1128/JVI.00584-17.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Thompson, E. A., Cascino, K., Ordonez, A. A., Zhou, W., Vaghasia, A., Hamacher-Brady, A., Brady, N. R., Sun, I. H., Wang, R., Rosenberg, A. Z., Delannoy, M., Rothman, R., Fenstermacher, K., Sauer, L., Shaw-Saliba, K., Bloch, E. M., Redd, A. D., Tobian, A. A. R., Horton, M., Smith, K., Pekosz, A., D'Alessio, F. R., Yegnasubramanian, S., Ji, H., Cox, A. L., and Powell, J. D. (2021) Metabolic programs define dysfunctional immune responses in severe COVID-19 patients, Cell Rep., 34, 108863, https://doi.org/10.1016/j.celrep.2021.108863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the Russian Science Foundation (project no. 20-15-00120).

Author information

Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Natalia V. Belosludtseva

  2. Mari State University, 424001, Yoshkar-Ola, Mari El, Russia

    Natalia V. Belosludtseva, Mikhail V. Dubinin & Konstantin N. Belosludtsev

Authors
  1. Natalia V. Belosludtseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mikhail V. Dubinin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Konstantin N. Belosludtsev
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.N.B. developed the concept of the review; N.V.B., M.V.D., and K.N.B. wrote the text of the article; N.V.B. and K.N.B. edited the manuscript; M.V.D. and K.N.B. prepared the illustrations.

Corresponding author

Correspondence to Konstantin N. Belosludtsev.

Ethics declarations

This work does not contain any studies involving human or animal subjects. The authors of this work declare that they have no conflict of interest.

Additional information

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Belosludtseva, N.V., Dubinin, M.V. & Belosludtsev, K.N. Pore-Forming VDAC Proteins of the Outer Mitochondrial Membrane: Regulation and Pathophysiological Role. Biochemistry Moscow 89, 1061–1078 (2024). https://doi.org/10.1134/S0006297924060075

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297924060075

Keywords

Search

Navigation