Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function
Open accessAbstract
Mitochondria play a central role in energy metabolism, Ca2+ signalling, aging and cell death. To control cytosolic or mitochondrial Ca2+ concentration, mitochondria possess several Ca2+-transport systems across the inner membrane. However, the pathway for Ca2+ crossing the outer membrane has not been directly addressed. We report that purified voltage-dependent anion channel (VDAC) reconstituted into lipid bilayers or liposomes is highly permeable to Ca2+. VDAC contains Ca2+-binding sites that bind Ruthenium Red (RuR), La3+ and that RuR completely closed VDACs in single or multichannel experiments. Energized, freshly prepared mitochondria accumulate Ca2+ (500–700nmol/mg of protein), and subsequently released it. The release of Ca2+ is accompanied by cyclosporin A-inhibited swelling, suggesting activation of permeability transition pore (PTP). RuR and ruthenium amine binuclear complex, when added to mitochondria after Ca2+ accumulation has reached a maximal level and before PTP is activated, prevented the release of Ca2+ and the accompanied mitochondrial swelling. RuR also prevented PTP opening promoted by atractyloside, an adenine nucleotide translocase inhibitor. These results suggest that VDAC, located in the mitochondrial outer membrane, controls Ca2+ transport into and from the mitochondria, and that the inhibition of Ca2+ uptake by RuR and La3+ may result from their interaction with VDAC Ca2+-binding sites. Inhibition of PTP opening or assembly by RuR and ruthenium amine binuclear complex suggest the involvement of VDAC in PTP activity and/or regulation. The permeability of VDAC to Ca2+ and its binding of Ca2+, suggest that VDAC has a role in regulation of the mitochondrial Ca2+ homoeostasis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
VDAC in the outer mitochondrial membrane is important for Ca2+ in- and outflux of mitochondria.
“It has been reported that VDAC located in the outer mitochondrial membrane is important for the in-and outflux of Ca 2ϩ of the mitochondria (43)”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [43]
Cited by
Sorted by citations
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
Calcium, ATP, and ROS: a mitochondrial love-hate triangle
Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W., & Sheu, S.-S. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00139.2004 · Cited by 2,575 · see citing works
“Ca(2) , recent studies suggest that the outer membrane voltagedependent anion channel (VDAC) is a ruthenium red (RuRed)sensitive Ca(2) channel and thus serves to regulate Ca(2) entry to mitochondrial intermembrane space (60).”
BackgroundChaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels
Szabadkai, G., Bianchi, K., Várnai, P., De Stefani, D., Wieckowski, M. R., Cavagna, D., Nagy, A. I., Balla, T., & Rizzuto, R. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200608073 · Cited by 1,413 · see citing works
“Based on previous observations (Gincel et al., 2001; Csordas et al., 2002; Rapizzi et al., 2002; Israelson et al., 2005), we used VDAC1 as the start point for proteomic search of interacting proteins and for unraveling the molecular basis of mitochondrial Ca2+ homeostasis.”
BackgroundMethodMitochondrial creatine kinase in human health and disease
Schlattner, U., Tokarska-Schlattner, M., & Wallimann, T. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2005.09.004 · Cited by 617 · see citing works
“Possibly, the calcium signal is perceived through the interaction partner VDAC, where a specific Ca binding site has been identified [87].”
Hajnóczky, G., Csordás, G., Das, S., Garcı́a-Pérez, C., Saotome, M., Roy, S. S., & Yi, M. (2006) · Cell Calcium · doi:10.1016/j.ceca.2006.08.016 · Cited by 613 · see citing works
“In regard to the specificity of the inhibition of the VDAC and UP it is relevant that RuRed also inhibits plasma membrane and intracellular cation channels (e.g. TASK-3[40], TRPV [41] and RyR[42], respectively).”
BackgroundInfluentialDeniaud, A., Sharaf el dein, O., Maillier, E., Poncet, D., Kroemer, G., Lemaire, C., & Brenner, C. (2008) · Oncogene · doi:10.1038/sj.onc.1210638 · Cited by 586 · see citing works
“In our cell-free system, we also used different inhibitors of VDAC to block the Ca2þ m entry through the OMM, as described earlier by Gincel et al. (2001).”
MethodBlalock, E. M., Chen, K.-C., Sharrow, K., Herman, J. P., Porter, N. M., Foster, T. C., & Landfield, P. W. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03807.2003 · Cited by 570 · see citing works
Role of the mitochondrial membrane permeability transition in cell death
Tsujimoto, Y., & Shimizu, S. (2006) · APOPTOSIS · doi:10.1007/s10495-006-0525-7 · Cited by 559 · see citing works
“logical properties of the PTP are strikingly similar to those of the VDAC incorporated in planar phospholipids bilayers [18, 19]; (2) various factors that alter VDAC channel properties, such as addition of NADH, Ca2+, or glutamate, as well as binding to hexokinase II [20–24], also modulate PTP activity [25–27]; and (3…”
BackgroundRasola, A., & Bernardi, P. (2007) · APOPTOSIS · doi:10.1007/s10495-007-0723-y · Cited by 507 · see citing works
“PTP [63, 64], and VDAC is modulated by many factors that also affect the PTP, such as NADH, Ca2+, glutamate and binding of hexokinase [65–69].”
Calcium signaling and apoptosis
Hajnóczky, G., Davies, E., & Madesh, M. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00616-8 · Cited by 462 · see citing works
Rapizzi, E., Pinton, P., Szabadkai, G., Wieckowski, M. R., Vandecasteele, G., Baird, G., Tuft, R. A., Fogarty, K. E., & Rizzuto, R. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200205091 · Cited by 453 · see citing works
“More recently, VDAC has been shown to be highly permeable to Ca(2) and to contain binding sites for ruthenium red that inhibit channel opening (Gincel et al., 2001).”
BackgroundMitochondrial calcium exchange in physiology and disease
Garbincius, J. F., & Elrod, J. W. (2021) · Physiological Reviews · doi:10.1152/physrev.00041.2020 · Cited by 413 · see citing works
Kapustin, A. N., Davies, J. D., Reynolds, J. L., McNair, R., Jones, G. T., Sidibe, A., Schurgers, L. J., Skepper, J. N., Proudfoot, D., Mayr, M., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.238808 · Cited by 417 · see citing works
The actin cytoskeleton: a key regulator of apoptosis and ageing?
Gourlay, C. W., & Ayscough, K. R. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1682 · Cited by 405 · see citing works
“35 ) and in the release of Ca 2+ from mitochondria into the cytoplas”
BackgroundChemotherapy: targeting the mitochondrial cell death pathway
Debatin, K., Poncet, D., & Kroemer, G. (2002) · Oncogene · doi:10.1038/sj.onc.1206039 · Cited by 398 · see citing works
Mitochondrial dysfunction in neurodegenerative disorders
Klemmensen, M. M., Borrowman, S. H., Pearce, C., Pyles, B., & Chandra, B. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2023.10.002 · Cited by 396 · see citing works
“The expression of this protein directly correlates with the rapid in fl ux of calcium into the mitochondria [84 – 86].”
BackgroundGAPDH, a novel regulator of the pro-apoptotic mitochondrial membrane permeabilization
Tarze, A., Deniaud, A., Bras, M. L., Maillier, E., Mollé, D., Larochette, N., Zamzami, N., Jan, G., Kroemer, G., & Brenner, C. (2006) · Oncogene · doi:10.1038/sj.onc.1210074 · Cited by 345 · see citing works
“, 2004) as well as calcium transport (Gincel et al., 2001) have been reported.”
BackgroundMitochondria-lysosome contacts regulate mitochondrial Ca 2+ dynamics via lysosomal TRPML1
Peng, W., Wong, Y. C., & Krainc, D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003236117 · Cited by 342 · see citing works
Mitochondria as therapeutic targets for cancer chemotherapy
Galluzzi, L., Larochette, N., Zamzami, N., & Kroemer, G. (2006) · Oncogene · doi:10.1038/sj.onc.1209598 · Cited by 342 · see citing works
Mitochondrial Channels: Ion Fluxes and More
Szabó, I., & Zoratti, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00021.2013 · Cited by 321 · see citing works
Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS
Israelson, A., Arbel, N., Cruz, S. D., Ilieva, H. S., Yamanaka, K., Shoshan‐Barmatz, V., & Cleveland, D. W. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.019 · Cited by 313 · see citing works
“(B) ADP and (C) Ca2+ accumulation were measured before and after the addition of 3 mM (50 mg/ml) hSOD1wt, hSOD1G93A, or hSOD1G85R purified proteins.”
BackgroundMethodInfluentialSelf-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
“Reconstitution of purified VDAC into a PLB, multichannel current recording and data analyses were carried out as described previously.(7) Briefly, PLB was prepared from soybean asolactin dissolved in n-decane (50 mg/ml) in a chamber containing 10 mM Hepes/KOH (pH 7.”
BackgroundMethodInfluentialSelf-citationVDAC closure increases calcium ion flux
Tan, W., & Colombini, M. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.06.002 · Cited by 281 · see citing works
“Indeed, in a recent study [6], the authors concluded that VDAC opening promotes calcium flux into mitochondria followed by PTP and mitochondrial swelling, i.”
BackgroundMessina, A. A., Reina, S., Guarino, F., & Pinto, V. D. (2011) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2011.10.005 · Cited by 269 · see citing works
Javadov, S. A., & Karmazyn, M. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000103747 · Cited by 281 · 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
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
“Several lines of evidence suggest that VDAC1 possesses divalent cation-binding site(s): (1) La and Tb, which are known to bind to Ca-binding proteins, induce channel closure when added to VDAC reconstituted into a PLB [117–119], (2) ruthenium red (RuR) [117, 121] and ruthenium amine binuclear complex (Ru360) [122], kn…”
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-citationOn the Role of VDAC in Apoptosis: Fact and Fiction
Rostovtseva, T. K., Tan, W., & Colombini, M. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-6566-8 · Cited by 242 · see citing works
“This important ion permeates through both the open (Gincel et al., 2001) and closed states (T.R. unpublished) of VDAC.”
BackgroundVDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases
Shoshan‐Barmatz, V., Shteinfer‐Kuzmine, A., & Verma, A. (2020) · Biomolecules · doi:10.3390/biom10111485 · Cited by 232 · see citing works
“The divalent cation-binding sites bind the lanthanides, La 3 + and Tb 3 + , as well as ruthenium red (RuR), and its analogue Ru360 [127–129], the photo-reactive analogue azido ruthenium (AzRu) [130].”
BackgroundSelf-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
“Reconstitution of purified native mVDAC1 and Δ(26)mVDAC1 into a planar lipid bilayer (PLB), channel recording, and analysis were carried out as described previously (Gincel et al., 2001).”
MethodSelf-citationProperties of the permeability transition in VDAC1−/− mitochondria
Krauskopf, A., Eriksson, O., Craigen, W. J., Forte, M. A., & Bernardi, P. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.02.007 · Cited by 230 · see citing works
“formation [7–17], an issue that was considerably strengthened by our identification of VDAC1 as the target for the high affinity inhibitor Ro 68-3400 [18].”
BackgroundBáthori, G., Csordás, G., Garcı́a-Pérez, C., Davies, E., & Hajnóczky, G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600906200 · Cited by 224 · see citing works
Oligomeric 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
“VDAC purification, reconstitution, channel-activity recording and analysis Voltage-dependent anion channel was purified as described in Gincel et al. (2001). VDAC was reconstituted into a planar lipid bilayer, recorded and analysed as described in AzoulayZohar et al.”
MethodInfluentialSelf-citationBid, but Not Bax, Regulates VDAC Channels
Rostovtseva, T. K., Antonsson, B. E., Suzuki, M., Youle, R. J., Colombini, M., & Bezrukov, S. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310593200 · Cited by 197 · see citing works
VDAC1: from structure to cancer therapy
Shoshan‐Barmatz, V., & Mizrachi, D. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00164 · Cited by 193 · see citing works
Self-citationUncovering 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-citationMitochondrial Regulation of Synaptic Plasticity in the Hippocampus
Levy, M., Faas, G. C., Saggau, P., Craigen, W. J., & Sweatt, J. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212878200 · Cited by 179 · see citing works
Mediation of the antiapoptotic activity of Bcl-xL protein upon interaction with VDAC1 protein
Arbel, N., Ben-Hail, D., & Shoshan-Barmatz, V. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.345918 · Cited by 179 · see citing works
“Single andmultiple channel current recording and data analysis were carried out as described previously (29).”
BackgroundMethodInfluentialSelf-citationLi, Y., Boehning, D. F., Qian, T., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7345com · Cited by 180 · see citing works
“The MCU inhibitors ruthenium red and Ru360 are known to specifically interact with the Ca2 binding site in VDAC (34, 35).”
BackgroundInfluentialHajnóczky, G., Csordás, G., & Yi, M. (2002) · Cell Calcium · doi:10.1016/s0143416002001872 · Cited by 172 · see citing works
Baik, S. H., Ramanujan, V. K., Becker, C. A., Fett, S., Underhill, D. M., & Wolf, A. J. (2023) · Science Immunology · doi:10.1126/sciimmunol.ade7652 · Cited by 178 · see citing works
Arbel, N., & Shoshan-Barmatz, V. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.082990 · Cited by 168 · see citing works
Self-citationSimvastatin Effects on Skeletal Muscle
Larsen, S., Stride, N., Hey-Mogensen, M., Hansen, C. N., Bang, L. E., Bundgaard, H., Nielsen, L. B., Helge, J. W., & Dela, F. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.09.036 · Cited by 165 · see citing works
Rimmerman, N., Ben-Hail, D., Porat, Z., Juknat, A., Kozela, E., Daniels, M. P., Connelly, P. S., Leishman, E., Bradshaw, H. B., Shoshan‐Barmatz, V., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.471 · Cited by 164 · see citing works
Self-citationKerkhofs, M., Bittremieux, M., Morciano, G., Giorgi, C., Pinton, P., Parys, J. B., & Bultynck, G. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0179-0 · Cited by 160 · see citing works
Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury
Shen, L., Gan, Q., Yang, Y., Reis, C., Zhang, Z., Xu, S., Zhang, T., & Sun, C. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.687246 · Cited by 157 · see citing works
Type 1 ryanodine receptor in cardiac mitochondria: Transducer of excitation–metabolism coupling
Beutner, G., Sharma, V. K., Lin, L., Ryu, S., Dirksen, R. T., & Sheu, S. (2005) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2005.09.016 · Cited by 161 · see citing works
VDAC1 functions in Ca2+ homeostasis and cell life and death in health and disease
Shoshan‐Barmatz, V., Krelin, Y., & Shteinfer‐Kuzmine, A. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.06.007 · Cited by 162 · see citing works
Self-citationMartin, E. M., Smeester, L., Bommarito, P. A., Grace, M. R., Boggess, K., Kuban, K., Karagas, M. R., Marsit, C. J., O’Shea, T. M., & Fry, R. C. (2017) · Epigenomics · doi:10.2217/epi-2016-0132 · Cited by 135 · see citing works
Mironov, S. L., Ivannikov, M. V., & Johansson, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409819200 · Cited by 157 · see citing works
Huntington’s Disease and Mitochondria
Farshbaf, M. J., & Ghaedi, K. (2017) · Neurotoxicity Research · doi:10.1007/s12640-017-9766-1 · Cited by 148 · see citing works
“Voltage-dependent anion channel (VDAC) is the main conductor for Ca passing through mitochondrial outer membrane (Gincel et al. 2001).”
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-citationSilencing VDAC1 Expression by siRNA Inhibits Cancer Cell Proliferation and Tumor Growth In Vivo
Arif, T., Vasilkovsky, L., Refaely, Y., Konson, A., & Shoshan‐Barmatz, V. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.9 · Cited by 148 · see citing works
Self-citationVDAC regulation of mitochondrial calcium flux: From channel biophysics to disease
Rosencrans, W. M., Rajendran, M., Bezrukov, S. M., & Rostovtseva, T. K. (2021) · Cell Calcium · doi:10.1016/j.ceca.2021.102356 · Cited by 142 · see citing works
“who were the first to demonstrate typical VDAC gating for channels reconstituted into pure 150/500 mM CaCl2 solutions [68].”
BackgroundVoltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics
Shoshan‐Barmatz, V., Krelin, Y., Shteinfer‐Kuzmine, A., & Arif, T. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00154 · Cited by 134 · see citing works
Self-citationMonaco, G., Decrock, E., Arbel, N., van Vliet, A. R., Rovere, R. M. L. L., SMEDT, H. D., Parys, J. B., Agostinis, P., Leybaert, L., Shoshan‐Barmatz, V., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.622514 · Cited by 134 · see citing works
“Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), ER-resident intracellular Ca(2) -release channels, are indirectly linked to the Ca(2) -permeable voltage-dependent anion channels (VDACs) (8, 9).”
BackgroundSelf-citationThe regulation of OXPHOS by extramitochondrial calcium
Gellerich, F. N., Gizatullina, Z. Z., Trumbeckaitė, S., Nguyen, H. P., Pallas, T., Arandarčikaitė, O., Vielhaber, S., Seppet, E. K., & Striggow, F. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.005 · Cited by 129 · see citing works
Nanotechnology inspired tools for mitochondrial dysfunction related diseases
Wen, R. M., Banik, B., Pathak, R., Kumar, A., Kolishetti, N., & Dhar, S. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.12.024 · Cited by 130 · see citing works
Salinas, T., Duchêne, A.-M., Delage, L., Nilsson, S., Glaser, E., Zaepfel, M., & Maréchal-Drouard, L. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0606449103 · Cited by 127 · see citing works
Yang, K.-T., Chang, W.-L., Yang, P.-C., Chien, C.-L., Lai, M.-S., Su, M., & Wu, M.-L. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401813 · Cited by 126 · see citing works
The Mitochondrial Voltage-Dependent Anion Channel 1, Ca2+ Transport, Apoptosis, and Their Regulation
Shoshan‐Barmatz, V., De, S., & Meir, A. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00060 · Cited by 122 · see citing works
Self-citationBano, D., & Ankarcrona, M. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.08.048 · Cited by 113 · see citing works
A role for TSPO in mitochondrial Ca2+ homeostasis and redox stress signaling
Gatliff, J., East, D. A., Singh, A., Álvarez, M. S., Frison, M., Matić, I., Ferraina, C., Sampson, N., Turkheimer, F., & Campanella, M. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.186 · Cited by 108 · see citing works
CGI1746 targets σ1R to modulate ferroptosis through mitochondria-associated membranes
Zhang, Z., Zhou, H., Gu, W., Wei, Y., Mou, S., Wang, Y., Zhang, J., & Zhong, Q. (2024) · Nature Chemical Biology · doi:10.1038/s41589-023-01512-1 · Cited by 125 · see citing works
“VDAC1 located at ER–mitochondria contact sites mediates Ca 2+ transfer into the intermembrane space from the high Ca 2+ microdomain formed by IP 3 R 36,37 .”
Subcellular localization of VDAC in mitochondria and ER in the cerebellum
Shoshan‐Barmatz, V., Zalk, R., Gincel, D., & Vardi, N. (2004) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2004.02.009 · Cited by 109 · see citing works
“The voltage-dependent anion channel (VDAC) controls the passage of adenine nucleotides [1], Ca + [2], and other metabolites [3] into and from mitochondria.”
BackgroundSelf-citationCa2+-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-citationNahon, E., Israelson, A., Abu-Hamad, S., & Shoshan-Barmatz, V. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.020 · Cited by 101 · see citing works
“However, these effects of fluoxetine on mitochondrial activities may result from interacting with VDAC and decreasing its conductance as a channel providing passage for Ca [19],”
BackgroundMethodInfluentialSelf-citationProbing the Outer Mitochondrial Membrane in Cardiac Mitochondria with Nanoparticles
Salnikov, V. V., Lukyanenko, Y., Frederick, C. A., Lederer, W. J., & Lukyanenko, V. I. (2006) · Biophysical Journal · doi:10.1529/biophysj.106.094318 · Cited by 100 · see citing works
“CATR binds the C-state of the adenine nucleotide translocator and stimulates the PT pore (6,47,48); whereas alamethicin forms giant pores through both mitochondrial membranes (49,50).”
BackgroundVoltage-dependent anion channels are a key factor of male fertility
Kwon, W., Park, Y.-J., Mohamed, E. A., & Pang, M. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.09.021 · Cited by 99 · see citing works
Intertwined and Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, and Diseases
Perkins, H. T., & Allan, V. (2021) · Cells · doi:10.3390/cells10092341 · Cited by 88 · see citing works
“In order to transfer Ca2+, a complex is formed between the ER-resident IP3R and voltagedependent anion channel 1 (VDAC1) in the outer mitochondrial membrane [161,163,164].”
BackgroundMitochondrial calcium channels
Hoppe, U. C. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.04.017 · Cited by 95 · see citing works
“The voltage dependent anion channel (VDAC) reconstituted in lipid bilayers was shown to conduct Ca in addition to monovalent ions [16].”
BackgroundGonzalez–Gronow, M., Kalfa, T. A., Johnson, C. E., Gawdi, G., & Pizzo, S. V. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303172200 · Cited by 94 · see citing works
Liu, H., Yuan, L., Yang, X., & Wang, K. (2003) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(03)00072-3 · Cited by 95 · see citing works
Hu, H., Guo, L., Overholser, J. P., & Wang, X. (2022) · Cells · doi:10.3390/cells11193174 · Cited by 97 · see citing works
“VDAC1 was shown to be highly permeable to Ca2+, and contains a binding site for ruthenium red, thereby inhibiting channel opening [96,97].”
BackgroundEnlargement and Contracture of C2-Ceramide Channels
Siskind, L. J., Davoody, A., Lewin, N., Marshall, S., & Colombini, M. (2003) · Biophysical Journal · doi:10.1016/s0006-3495(03)74588-3 · Cited by 92 · see citing works
“La(13) is a known inhibitor of various types of channels and transporters (Takata et al., 1966; Reed and Bygrave, 1974; Armstrong and Cota, 1990; Sparagna et al., 1995; Colvin, 1998; Colvin et al., 2000; Gincel et al., 2001).”
BackgroundInfluentialAnion Channels of Mitochondria
Ponnalagu, D., & Singh, H. (2016) · Handbook of experimental pharmacology · doi:10.1007/164_2016_39 · Cited by 87 · see citing works
“All the cells from prokaryotes to eukaryotes maintain a cytosolic pH of ~7.2, with concentration of potassium ions (K+) many fold higher than sodium (Na+) Correspondence to: Harpreet Singh. uthor M anuscript A uthor M anuscript A uthor M anuscript and calcium (Ca2+) ions (Bose et al. 2015; Prindle et al. 2015).”
BackgroundInfluentialMultistep and multitask Bax activation
Ghibelli, L., & Diederich, M. F. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.08.003 · Cited by 84 · see citing works
“VDAC pore is regulated by physico-chemical mechanisms such as voltage, which is maintained by trans-membrane potential, and by molecular mechanisms including phosphorylation and binding by cytosolic proteins (Chen et al., 2010; Gincel et al., 2001).”
BackgroundMitochondria and Energetic Depression in Cell Pathophysiology
Seppet, E. K., Puurand, M., Peetsalu, A., Gizatullina, Z. Z., Nguyen, H. P., Vielhaber, S., Wussling, M. H. P., Trumbeckaitė, S., Arandarčikaitė, O., Jerzembek, D., et al. (2009) · International Journal of Molecular Sciences · doi:10.3390/ijms10052252 · Cited by 83 · see citing works
Shoshan‐Barmatz, V., & Israelson, A. (2005) · The Journal of Membrane Biology · doi:10.1007/s00232-005-0749-4 · Cited by 83 · see citing works
“... [32, 80], in SR, the organometallic hexavalent dye RuR and ruthenium amine binuclear complex, Ru360, known to specifically interact with Ca 2+ -binding proteins [80], induce VDAC channel closure in a time-dependent manner, and stabilize the channel in a completelyclosed state (Fig. 2). Thus, VDAC, as Ca 2+ transpo…”
InfluentialSelf-citationBouyer, G., Cueff, A., Égée, S., Kmiecik, J., Maksimova, Y. D., Glogowska, E., Gallagher, P. G., & Thomas, S. L. Y. (2011) · Blood · doi:10.1182/blood-2011-01-329300 · Cited by 79 · see citing works
VDAC1-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-citationMitochondrial calcium at the synapse
Datta, S., & Jaiswal, M. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.04.006 · Cited by 73 · see citing works
Localization of the voltage-dependent anion channel-1 Ca2+-binding sites
Israelson, A., Abu‐Hamad, S., Zaid, H., Nahon, E., & Shoshan‐Barmatz, V. (2006) · Cell Calcium · doi:10.1016/j.ceca.2006.06.005 · Cited by 79 · see citing works
“Similar to RuR [7] and Ru360 [8], AzRu decreased the hannel conductance of purified VDAC reconstituted into a lanar lipid bilayer (Fig.”
InfluentialSelf-citationIntracellular Ca2 + Imbalance Critically Contributes to Paraptosis
Kim, E., Lee, D. M., Seo, M. J., Lee, H. J., & Choi, K. S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.607844 · Cited by 80 · see citing works
Sander, P., Gudermann, T. W., & Schredelseker, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020946 · Cited by 79 · see citing works
“This was based on several lines of evidence: (i) a Ca2+ induced shift in electrophoretic mobility of VDAC1, (ii) a blockade of the channel by La3+, which could be reversed by the addition of EGTA, and (iii) an inhibition of the channel by ruthenium derivatives such as RuR, Ru360 [3], or AzRu [56] that was reversed by…”
BackgroundMethodMitochondrial ryanodine receptors and other mitochondrial Ca2+ permeable channels
Ryu, S.-Y., Beutner, G., Dirksen, R. T., Kinnally, K. W., & Sheu, S. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.032 · Cited by 80 · see citing works
“Both VDAC cationic and anionic conductance states are blocked by ruthenium red and lanthanides [60,68].”
BackgroundTikunov, A. P., Johnson, C. B., Pediaditakis, P., Markevich, N. I., Macdonald, J. M., Lemasters, J. J., & Holmuhamedov, E. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.01.008 · Cited by 74 · see citing works
Mitostasis, Calcium and Free Radicals in Health, Aging and Neurodegeneration
Godoy, J. A., Ríos, J. A., Picón-Pagès, P., Herrera-Fernández, V., Swaby, B., Crepin, G., Vicente, R., Fernández‐Fernández, J. M., & Muñoz, F. J. (2021) · Biomolecules · doi:10.3390/biom11071012 · Cited by 73 · see citing works
“The alteration of MAMs yields to the lack of Ca 2+ homeostasis and mitochondrial biogenesis impairment [97,116,120,121].”
BackgroundFunctional interaction of endothelial nitric oxide synthase with a voltage-dependent anion channel
Sun, J., & Liao, J. K. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202260999 · Cited by 72 · see citing works
C-terminal Lysines Determine Phospholipid Interaction of Sarcomeric Mitochondrial Creatine Kinase
Schlattner, U., Gehring, F., Vernoux, N., Tokarska-Schlattner, M., Neumann, D., Marcillat, O., Vial, C., & Wallimann, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314158200 · Cited by 71 · see citing works
Antonenkov, V. D., Isomursu, A., Mennerich, D., Vapola, M. H., Weiher, H., Kietzmann, T., & Hiltunen, J. K. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.608083 · Cited by 69 · see citing works
“An estimation of the Ca(2) /Cl permeability ratio was done as described (20).”
MethodJang, B., Kim, E., Choi, J.-K., et al. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080388 · Cited by 70 · see citing works
VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
Heslop, K. A., Milesi, V., & Maldonado, E. N. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.742839 · Cited by 72 · see citing works
Peroxisomal plant metabolism – an update on nitric oxide, Ca2+ and the NADPH recycling network
Corpas, F. J., & Barroso, J. B. (2017) · Journal of Cell Science · doi:10.1242/jcs.202978 · Cited by 65 · see citing works
“Ca can move through membranes using voltage-dependent anion channels, among others (Gincel et al., 2001; Jammes et al., 2011).”
BackgroundRegulation of mitochondrial calcium in plants versus animals
Wagner, S., Bortoli, S. D., Schwarzländer, M., & Szabó, I. (2016) · Journal of Experimental Botany · doi:10.1093/jxb/erw100 · Cited by 66 · see citing works
Endoplasmic Reticulum–Mitochondria Contact Sites—Emerging Intracellular Signaling Hubs
Aoyama-Ishiwatari, S., & Hirabayashi, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.653828 · Cited by 63 · see citing works
Regulation of ceramide channel formation and disassembly: Insights on the initiation of apoptosis
Abou-Ghali, M., & Stiban, J. (2015) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2015.03.005 · Cited by 64 · see citing works
“Apoptosis often occurs as a result of a variety of factors, for instance DNA damage (Wang, 2001); cellular stress (Samali et al., 2010; Fulda et al., 2010); disruption of calcium homeostasis (Preston et al., 1997); the closure of the voltage-dependent anion channel (VDAC) which inhibits the metabolic exchange between…”
BackgroundInfluentialRegulation of Ca2+ signalling and Ca2+-mediated cell death by the transcriptional coactivator PGC-1α
Bianchi, K., Vandecasteele, G., Carli, C., Romagnoli, A., Szabadkai, G., & Rizzuto, R. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401784 · Cited by 60 · see citing works
“The composite Ca2þ uptake system of the mitochondrial membranes comprises the voltage-dependent anion channel of the outer membrane and the Ca2þ uniporter (mitochondrial Ca2þ uniporter (MCU)) in the inner membrane.(7,8) Mitochondrial Ca2þ uptake is tightly dependent on the potential gradient (DCm,B 180 mV, negative in…”
Background
- Authors
- GINCEL, D., ZAID, H., & SHOSHAN-BARMATZ, V.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Department of Life Sciences and Zlotowski Center for Neuroscience, Ben Gurion University of the Negev, Beer Sheva, P.O.B. 653, 84105 Israel
- ORCID
- ZAID, Hilal
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2001-08-08
- Volume
- 358
- Issue
- 1
- Pages
- 147-155
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1222042
- OpenAlex
- W2012135330
- Cited by
- 396
- References
- 0
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 15 · 2023: 9 · 2022: 18 · 2021: 28 · 2020: 14 · 2019: 12 · 2018: 12 · 2017: 21 · 2016: 22 · 2015: 9 · 2014: 19 · 2013: 14 · 2012: 20
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- voltage-dependent anion channel, mitochondrial outer membrane, calcium transport, calcium binding sites, ruthenium red, lanthanum, mitochondrial permeability transition pore, mitochondrial calcium homeostasis, mitochondrial swelling, cyclosporine, atractyloside, adenine nucleotide translocase, calcium release
- MeSH terms
- Animals, Anions, Binding Sites, Calcium, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Humans, Intracellular Membranes, Ion Channels, Kinetics, Lanthanum, Lipid Bilayers, Liposomes, Mitochondria, Mitochondria, Liver, Models, Biological, Protein Binding, Ruthenium Red, Time Factors, Models, Statistical, Signal Transduction, Cyclosporine, Porins, Voltage-Dependent Anion Channels, Rats
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 ›
Are you an author, or do you see a problem with this page? Request a review
