Novel Compounds Targeting the Mitochondrial Protein VDAC1 Inhibit Apoptosis and Protect against Mitochondrial Dysfunction
Open accessAbstract
Apoptosis is thought to play a critical role in several pathological processes, such as neurodegenerative diseases ( i.e. Parkinson's and Alzheimer's diseases) and various cardiovascular diseases. Despite the fact that apoptotic mechanisms are well defined, there is still no substantial therapeutic strategy to stop or even slow this process. Thus, there is an unmet need for therapeutic agents that are able to block or slow apoptosis in neurodegenerative and cardiovascular diseases. The outer mitochondrial membrane protein voltage-dependent anion channel 1 (VDAC1) is a convergence point for a variety of cell survival and death signals, including apoptosis. Recently, we demonstrated that VDAC1 oligomerization is involved in mitochondrion-mediated apoptosis. Thus, VDAC1 oligomerization represents a prime target for agents designed to modulate apoptosis. Here, high-throughput compound screening and medicinal chemistry were employed to develop compounds that directly interact with VDAC1 and prevent VDAC1 oligomerization, concomitant with an inhibition of apoptosis as induced by various means and in various cell lines. The compounds protected against apoptosis-associated mitochondrial dysfunction, restoring dissipated mitochondrial membrane potential, and thus cell energy and metabolism, decreasing reactive oxidative species production, and preventing detachment of hexokinase bound to mitochondria and disruption of intracellular Ca 2+ levels. Thus, this study describes novel drug candidates with a defined mechanism of action that involves inhibition of VDAC1 oligomerization, apoptosis, and mitochondrial dysfunction. The compounds VBIT-3 and VBIT-4 offer a therapeutic strategy for treating different diseases associated with enhanced apoptosis and point to VDAC1 as a promising target for therapeutic intervention.
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The outer membrane transporter VDAC controls mPTP activity.
“In particular, the outer membrane transporter VDAC has been shown, by several studies, to control mPTP activity [6,22,23,24,25,26,27].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [23]
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009
Kroemer, G., Galluzzi, L., Vandenabeele, P., Abrams, J., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., El-Deiry, W. S., Golstein, P., Green, D. R., et al. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.150 · Cited by 3,399 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
The mitochondrial permeability transition pore and its role in cell death
CROMPTON, M. (1999) · Biochemical Journal · doi:10.1042/bj3410233 · Cited by 2,432 · see citing works
Johnstone, R. W., Ruefli, A. A., & Lowe, S. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00625-6 · Cited by 2,236 · see citing works
The mitochondrial membrane potential (Δψm) in apoptosis; an update
Ly, J. D., Grubb, D. R., & Lawen, A. (2003) · APOPTOSIS · doi:10.1023/a:1022945107762 · Cited by 1,599 · see citing works
Protein-binding assays in biological liquids using microscale thermophoresis
Wienken, C. J., Baaske, P., Rothbauer, U., Braun, D., & Duhr, S. (2010) · Nature Communications · doi:10.1038/ncomms1093 · Cited by 1,145 · see citing works
Apoptosis and Caspases in Neurodegenerative Diseases
Friedlander, R. M. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022366 · Cited by 873 · see citing works
Chen, G.-Q., Zhu, J., Shi, X., Ni, J., Zhong, H., Si, G., Jin, X., Tang, W., Li, X., Xong, S., et al. (1996) · Blood · doi:10.1182/blood.v88.3.1052.1052 · Cited by 863 · see citing works
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death
Kroemer, G., El-Deiry, W. S., Golstein, P., Peter, M. E., Vaux, D., Vandenabeele, P., Zhivotovsky, B., Blagosklonny, M. V., Malorni, W., Knight, R. A., et al. (2005) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401724 · Cited by 843 · see citing works
VDAC, a multi-functional mitochondrial protein regulating cell life and death
Shoshan‐Barmatz, V., Pinto, V. D., Zweckstetter, M., Raviv, Z., Keinan, N., & Arbel, N. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.03.002 · Cited by 792 · see citing works
Self-citationArsenic Trioxide Controls the Fate of the PML-RARα Oncoprotein by Directly Binding PML
Zhang, X., Yan, X.-J., Zhou, Z., Yang, F., Wu, Z., Sun, H., Liang, W., Song, A., Lallemand-Breitenbach, V., Jeanne, M., et al. (2010) · Science · doi:10.1126/science.1183424 · Cited by 785 · see citing works
Mitochondrial Binding of Hexokinase II Inhibits Bax-induced Cytochrome c Release and Apoptosis
Pastorino, J. G., Shulga, N., & Hoek, J. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109950200 · Cited by 714 · see citing works
The permeability transition pore complex: another view
Halestrap, A. P., McStay, G. P., & Clarke, S. J. (2002) · Biochimie · doi:10.1016/s0300-9084(02)01375-5 · Cited by 709 · see citing works
Solution structure of the integral human membrane protein VDAC-1 in detergent micelles
Hiller, S., Garces, R. G., Malia, T. J., Orekhov, V. Y., Colombini, M., & Wagner, G. (2008) · Science · doi:10.1126/science.1161302 · Cited by 667 · see citing works
The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet
Loo, G., Saelens, X., van Gurp, M., MacFarlane, M., Martin, S. J., & Vandenabeele, P. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401088 · Cited by 665 · see citing works
Apoptosis and Oxidative Stress in Neurodegenerative Diseases
Radi, E., Formichi, P., Battisti, C., & Federico, A. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132738 · Cited by 632 · see citing works
Structure of the human voltage-dependent anion channel
Bayrhuber, M., Meins, T., Habeck, M., Becker, S., Giller, K., Villinger, S., Vonrhein, C., Griesinger, C., Zweckstetter, M., & Zeth, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808115105 · Cited by 588 · see citing works
Myocytes Die by Multiple Mechanisms in Failing Human Hearts
Kostin, S., Pool, L., Elsässer, A., Hein, S., Drexler, H. C. A., Arnon, E., Hayakawa, Y., Zimmermann, R., Bauer, E., Klövekorn, W.-P., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000067471.95890.5c · Cited by 564 · see citing works
Ujwal, R., Cascio, D., Colletier, J., Faham, S., Zhang, J., Toro, L., Ping, P., & Abramson, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809634105 · Cited by 546 · see citing works
Cytochrome c Promotes Caspase-9 Activation by Inducing Nucleotide Binding to Apaf-1
Jiang, X., & Wang, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000405200 · Cited by 506 · see citing works
Voltage-dependent anion channel (VDAC) as mitochondrial governator—Thinking outside the box
Lemasters, J. J., & Holmuhamedov, E. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2005.10.006 · Cited by 437 · see citing works
Bernardi, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00041-2 · Cited by 412 · see citing works
AZOULAY-ZOHAR, H., ISRAELSON, A., ABU-HAMAD, S., & SHOSHAN-BARMATZ, V. (2004) · Biochemical Journal · doi:10.1042/bj20031465 · Cited by 408 · see citing works
Self-citationPastorino, J. G., Hoek, J. B., & Shulga, N. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1925 · Cited by 398 · see citing works
Regulation of hexokinase binding to VDAC
Pastorino, J. G., & Hoek, J. B. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9148-8 · Cited by 388 · see citing works
Essential Role of Voltage-Dependent Anion Channel in Various Forms of Apoptosis in Mammalian Cells
Shimizu, S., Matsuoka, Y., Shinohara, Y., Yoneda, Y., & Tsujimoto, Y. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.2.237 · Cited by 367 · see citing works
Manczak, M., & Reddy, P. H. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds360 · Cited by 348 · see citing works
Cytochrome c release from mitochondria: all or nothing
Martinou, J., Desagher, S., & Antonsson, B. E. (2000) · Nature Cell Biology · doi:10.1038/35004069 · Cited by 320 · see citing works
Shoshan‐Barmatz, V., Israelson, A., Brdiczka, D. G., & Sheu, S. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206777585111 · Cited by 307 · see citing works
Self-citationThe voltage-dependent anion channel-1 modulates apoptotic cell death
Zaid, H., Abu‐Hamad, S., Israelson, A., Nathan, I., & Shoshan‐Barmatz, V. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401599 · Cited by 299 · see citing works
Self-citationObulesu, M., & Lakshmi, M. J. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1454-4 · Cited by 290 · see citing works
Abu-Hamad, S., Zaid, H., Israelson, A., Nahon, E., & Shoshan-Barmatz, V. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708216200 · Cited by 278 · see citing works
Baumgartner, H. K., Gerasimenko, J. V., Thorne, C., Ferdek, P. E., Pozzan, T., Tepikin, A. V., Petersen, O. H., Sutton, R., Watson, A. J. M., & Gerasimenko, O. V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025353 · Cited by 276 · see citing works
Keinan, N., Tyomkin, D., & Shoshan‐Barmatz, V. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00165-10 · Cited by 269 · see citing works
Self-citationde Jong, A. M., Maass, A. H., Oberdorf‐Maass, S. U., van Veldhuisen, D. J., van Gilst, W. H., & Gelder, I. C. V. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq357 · Cited by 266 · see citing works
The voltage-dependent anion channel: an essential player in apoptosis
Tsujimoto, Y., & Shimizu, S. (2002) · Biochimie · doi:10.1016/s0300-9084(02)01370-6 · Cited by 251 · see citing works
VDAC, a multi-functional mitochondrial protein as a pharmacological target
Shoshan‐Barmatz, V., & Ben-Hail, D. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.04.001 · Cited by 250 · see citing works
Self-citationThe mitochondrial voltage-dependent anion channel 1 in tumor cells
Shoshan‐Barmatz, V., Ben-Hail, D., Admoni, L., Krelin, Y., & Tripathi, S. S. (2014) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2014.10.040 · Cited by 245 · see citing works
Self-citationThe expression level of the voltage-dependent anion channel controls life and death of the cell
Abu‐Hamad, S., Sivan, S., & Shoshan‐Barmatz, V. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600103103 · Cited by 240 · see citing works
Self-citationAbu-Hamad, S., Arbel, N., Calo, D., Arzoine, L., Israelson, A., Keinan, N., Ben-Romano, R., Friedman, O., & Shoshan-Barmatz, V. (2009) · Journal of Cell Science · doi:10.1242/jcs.040188 · Cited by 226 · see citing works
Self-citationOligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria
Zalk, R., Israelson, A., GARTY, E. S., Azoulay‐Zohar, H., & Shoshan‐Barmatz, V. (2005) · Biochemical Journal · doi:10.1042/bj20041356 · Cited by 222 · see citing works
Self-citationMethyl jasmonate binds to and detaches mitochondria-bound hexokinase
Goldin, N., Arzoine, L., Heyfets, A., Israelson, A., Zaslavsky, Z., Bravman, T., Bronner, V., Notcovich, A., Shoshan‐Barmatz, V., & Flescher, E. (2008) · Oncogene · doi:10.1038/onc.2008.108 · Cited by 208 · see citing works
Self-citationHierarchical involvement of Bak, VDAC1 and Bax in cisplatin-induced cell death
Tajeddine, N., Galluzzi, L., Kepp, O., Hangen, E., Morselli, E., Senovilla, L., Araujo, N., Pinna, G., Larochette, N., Zamzami, N., et al. (2008) · Oncogene · doi:10.1038/onc.2008.63 · Cited by 207 · see citing works
Zheng, Y., Shi, Y., Tian, C., Jiang, C., Jin, H., Chen, J., Almasan, A., Tang, H., & Chen, Q. (2003) · Oncogene · doi:10.1038/sj.onc.1207205 · Cited by 202 · see citing works
Uncovering the role of VDAC in the regulation of cell life and death
Shoshan‐Barmatz, V., Keinan, N., & Zaid, H. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9147-9 · Cited by 179 · see citing works
Self-citationThe BRET technology and its application to screening assays
Bacart, J., Corbel, C., Jockers, R., Bach, S., & Couturier, C. (2008) · Biotechnology Journal · doi:10.1002/biot.200700222 · Cited by 178 · see citing works
The Supramolecular Assemblies of Voltage-dependent Anion Channels in the Native Membrane
Hoogenboom, B. W., Suda, K., Engel, A. H., & Fotiadis, D. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.04.073 · Cited by 174 · see citing works
Arzoine, L., Zilberberg, N., Ben-Romano, R., & Shoshan‐Barmatz, V. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803614200 · Cited by 173 · see citing works
Self-citationTargeting VDAC-bound hexokinase II: a promising approach for concomitant anti-cancer therapy
Krasnov, G. S., Dmitriev, A. A., Lakunina, V. A., Кирпий, А. А., & Kudryavtseva, A. V. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.833607 · Cited by 167 · see citing works
VDAC is a conserved element of death pathways in plant and animal systems
Godbole, A., Varghese, J., Sarin, A., & Mathew, M. K. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00102-2 · Cited by 162 · see citing works
Supramolecular Assembly of VDAC in Native Mitochondrial Outer Membranes
Gonçalves, R. P., Buzhynskyy, N., Prima, V., Sturgis, J. N., & Simon Scheuring, A. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.03.063 · Cited by 157 · see citing works
Shoshan‐Barmatz, V., Keinan, N., Abu‐Hamad, S., Tyomkin, D., & Aram, L. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.03.003 · Cited by 147 · see citing works
Self-citationDoran, E., & Halestrap, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480343 · Cited by 139 · see citing works
Key regions of VDAC1 functioning in apoptosis induction and regulation by hexokinase
Shoshan‐Barmatz, V., Zakar, M., Rosenthal, K., & Abu‐Hamad, S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.11.009 · Cited by 139 · see citing works
Self-citationMitochondrial VDAC1: Function in Cell Life and Death and a Target for Cancer Therapy
Shoshan‐Barmatz, V., & Golan, M. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712798992110 · Cited by 139 · see citing works
Self-citationCuadrado‐Tejedor, M., Vilariño, M., Cabodevilla, F., Río, J. D., Frechilla, D., & Pérez‐Mediavilla, A. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100966 · Cited by 134 · see citing works
Bertrand, L., Parent, S., Caron, M., Legault, M., Joly, E. C., Angers, S., Bouvier, M., Brown, M., Houle, B., & Ménard, L. (2002) · Journal of Receptors and Signal Transduction · doi:10.1081/rrs-120014619 · Cited by 129 · see citing works
The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis
Keinan, N., Pahima, H. T., Ben-Hail, D., & Shoshan‐Barmatz, V. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.03.017 · Cited by 116 · see citing works
Self-citationAtrial Fibrillation in Heart Failure: A Comprehensive Review
DEEDWANIA, P. C., & Lardizabal, J. A. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.06.033 · Cited by 115 · see citing works
The Role of Lipids in VDAC Oligomerization
Betaneli, V., Petrov, E. P., & Schwille, P. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2011.12.049 · Cited by 113 · see citing works
Ca2+-mediated regulation of VDAC1 expression levels is associated with cell death induction
Algor, S. W., Keinan, N., Ben-Hail, D., Arif, T., & Shoshan‐Barmatz, V. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.03.021 · Cited by 106 · see citing works
Self-citationRegenold, W. T., Pratt, M., Nekkalapu, S., Shapiro, P. S., Kristián, T., & Fiskum, G. M. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.09.018 · Cited by 96 · see citing works
Amyloid-β Triggers the Release of Neuronal Hexokinase 1 from Mitochondria
Saraiva, L. M., Seixas da Silva, G. S., Galina, A., da-Silva, W. S., Klein, W. L., Ferreira, S. T., & De Felice, F. G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015230 · Cited by 94 · see citing works
Reina, S., Checchetto, V., Saletti, R., Gupta, A., Chaturvedi, D., Guardiani, C., Guarino, F., Scorciapino, M. A., Magrì, A., Foti, S., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.6850 · Cited by 91 · see citing works
Self-citationOligomerization of the Mitochondrial Protein VDAC1
Shoshan‐Barmatz, V., Mizrachi, D., & Keinan, N. (2013) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-386931-9.00011-8 · Cited by 87 · see citing works
Self-citationRole of cysteines in mammalian VDAC isoforms' function
Pinto, V. D., Reina, S., Gupta, A., Messina, A. A., & Mahalakshmi, R. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.02.020 · Cited by 84 · see citing works
Self-citationVDAC1-interacting anion transport inhibitors inhibit VDAC1 oligomerization and apoptosis
Ben-Hail, D., & Shoshan-Barmatz, V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.04.002 · Cited by 80 · see citing works
Self-citationApoptosis commitment – translating survival signals into decisions on mitochondria
Keeble, J. A., & Gilmore, A. P. (2007) · Cell Research · doi:10.1038/cr.2007.101 · Cited by 78 · see citing works
Mitochondrial hexokinase HKI is a novel substrate of the Parkin ubiquitin ligase
Okatsu, K., Iemura, S., Koyano, F., Go, E., Kimura, M., Natsume, T., Tanaka, K., & Matsuda, N. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.10.041 · Cited by 77 · see citing works
Scharstuhl, A., Mutsaers, H. A. M., Pennings, S. W. C., Rüssel, F. G. M., & Wagener, F. A. D. T. G. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006688 · Cited by 76 · see citing works
Dystrophic neurites of senile plaques in Alzheimer’s disease are deficient in cytochrome c oxidase
Pérez-Gracia, E., Torrejón-Escribano, B., & Ferrer, I. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0370-6 · Cited by 72 · see citing works
Ahmed, M., Muhammed, S. J., Kessler, B. M., & Salehi, A. A. (2010) · Islets · doi:10.4161/isl.2.5.12639 · Cited by 69 · see citing works
Matter of Life and Death: the Pharmacological Approaches Targeting Apoptosis in Brain Diseases
Cavallucci, V., & D’Amelio, M. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211795049705 · Cited by 67 · see citing works
Branco, A. F., Pereira, S. L., Moreira, A. C., Holy, J. M., Sardão, V. A., & Oliveira, P. J. (2011) · Cardiovascular Toxicology · doi:10.1007/s12012-011-9111-5 · Cited by 64 · see citing works
A Role for Voltage-Dependent Anion Channel Vdac1 in Polyglutamine-Mediated Neuronal Cell Death
Ghosh, T., Pandey, N., Maitra, A., Brahmachari, S. K., & Pillai, B. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001170 · Cited by 63 · see citing works
A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells
Huang, L., Han, J., Ben-Hail, D., He, L., Li, B., Chen, Z., Wang, Y., Yang, Y., Liu, L., Zhu, Y., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.648774 · Cited by 56 · see citing works
Self-citationUjwal, R., Cascio, D., Chaptal, V., Ping, P., & Abramson, J. (2009) · Channels · doi:10.4161/chan.3.3.9196 · Cited by 54 · see citing works
Shan, D., Mount, D., Moore, S., Haroutunian, V. H., Meador‐Woodruff, J. H., & McCullumsmith, R. E. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.01.028 · Cited by 50 · see citing works
Antiapoptotic Drugs: A Therapautic Strategy for the Prevention of Neurodegenerative Diseases
Sureda, F. X., Junyent, F., Verdaguer, E., Auladell, C., Pelegrı́, C., Vilaplana, J., Folch, J., Canudas, A. M., Zárate, C. B., Pallàs, M., et al. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211795049732 · Cited by 49 · see citing works
VDAC1 cysteine residues: topology and function in channel activity and apoptosis
Aram, L., Geula, S., Arbel, N., & Shoshan‐Barmatz, V. (2010) · Biochemical Journal · doi:10.1042/bj20091690 · Cited by 47 · see citing works
Self-citationDeletion of β-strands 9 and 10 converts VDAC1 voltage-dependence in an asymmetrical process
Reina, S., Magrì, A., Lolicato, M., Guarino, F., Impellizzeri, A. A. R., Maier, E., Benz, R., Ceccarelli, M., Pinto, V. D., & Messina, A. A. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.03.007 · Cited by 41 · see citing works
Self-citationCell Death in the Cardiac Myocyte
Marunouchi, T., & Tanonaka, K. (2015) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b15-00288 · Cited by 38 · see citing works
Functional Characterization of a Second Porin Isoform in Drosophila melanogaster
Aiello, R., Messina, A. A., Schiffler, B., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310572200 · Cited by 38 · see citing works
Rohn, T. T., Kokoulina, P., Eaton, C. R., & Poon, W. W. (2009) · PubMed Central · Cited by 36 · see citing works
Yu, J., Qian, H., Li, Y., et al. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.4.3887 · Cited by 33 · see citing works
Arsenic trioxide mechanisms of action – looking beyond acute promyelocytic leukemia
Carney, D. A. (2008) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190802464745 · Cited by 26 · see citing works
Purification of VDAC1 from Rat Liver MitochondriaPreprint
Ben-Hail, D., & Shoshan‐Barmatz, V. (2013) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot073130 · Cited by 21 · see citing works
Self-citationApproaching the structure of human VDAC1, a key molecule in mitochondrial cross-talk
Zeth, K., Meins, T., & Vonrhein, C. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9144-z · Cited by 19 · see citing works
Müller, P., Deneke, T., Schiedat, F., Bösche, L., Strauch, J., Dietrich, J. W., Vogt, M., Tannapfel, A., Stiegler, H., Mügge, A., et al. (2013) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12191 · Cited by 19 · see citing works
Reconstitution of Purified VDAC1 into a Lipid Bilayer and Recording of Channel ConductancePreprint
Ben-Hail, D., & Shoshan‐Barmatz, V. (2013) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot073148 · Cited by 8 · see citing works
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VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease
Kim, J., Gupta, R., Blanco, L. P., Yang, S., Shteinfer-Kuzmine, A., Wang, K., Zhu, J., Yoon, H. E., Wang, X., Kerkhofs, M., et al. (2019) · Science · doi:10.1126/science.aav4011 · Cited by 793 · see citing works
Self-citationVDAC1, mitochondrial dysfunction, and Alzheimer’s disease
Shoshan-Barmatz, V., Nahon-Crystal, E., Shteinfer-Kuzmine, A., & Gupta, R. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.010 · Cited by 286 · see citing works
Self-citationZhang, E., Mohammed Al-Amily, I., Mohammed, S., Luan, C., Asplund, O., Ahmed, M., Ye, Y., Ben-Hail, D., Soni, A., Vishnu, N., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.008 · Cited by 171 · see citing works
“…et al., 2010 PercevalHR Addgene 49,082 The multiple kinase inhibitor (MRT1) In-house-made Clark et al., 2012 VBIT-4 and AKOS-02 In-house-made Ben-Hail et al., 2016 Resveratrol AK Scientific 170134-5G Metformin Sigma-Aldrich D150959-5G N-Acetyl cysteine Sigma-Aldrich…”
BackgroundMethodInfluentialVDAC1 at the crossroads of cell metabolism, apoptosis and cell stress
Shoshan-Barmatz, V., N. Maldonado, E., & Krelin, Y. (2017) · Cell Stress · doi:10.15698/cst2017.10.104 · Cited by 170 · see citing works
Self-citationThe mitochondrial permeability transition: Nexus of aging, disease and longevity
Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
- Authors
- Ben-Hail, D., Begas-Shvartz, R., Shalev, M., Shteinfer-Kuzmine, A., Gruzman, A., Reina, S., De Pinto, V., & Shoshan-Barmatz, V.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Bar-Ilan University (IL)
- University of Catania (IT)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 291
- Issue
- 48
- Pages
- 24986-25003
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC5122769
- OpenAlex
- W2529946706
- Cited by
- 158
- References
- 92
- Citations by year
- 2026: 24 · 2025: 33 · 2024: 19 · 2023: 20 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 8 · 2018: 8 · 2017: 13
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
- Keywords
- VDAC1, apoptosis inhibition, mitochondrial dysfunction, VDAC1 oligomerization, mitochondrial outer membrane, mitochondrial membrane potential, reactive oxygen species, hexokinase, intracellular calcium, neurodegenerative diseases, cardiovascular disease, drug candidates
- MeSH terms
- Animals, Energy Metabolism, HeLa Cells, Humans, Mitochondria, Apoptosis, Mice, Knockout, Calcium Signaling, Voltage-Dependent Anion Channel 1, Mice, Rats, Protein Multimerization, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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