voltage dependent anion channels


Summary: A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.

Top Publications

  1. Wang K, Kondo H, Hirono I, Aoki T. The Marsupenaeus japonicus voltage-dependent anion channel (MjVDAC) protein is involved in white spot syndrome virus (WSSV) pathogenesis. Fish Shellfish Immunol. 2010;29:94-103 pubmed publisher
    ..dsRNA silencing of shrimp VDAC delayed white spot syndrome virus (WSSV) infection by 1 day in different shrimp organs. Taken together, these findings suggest that MjVDAC is likely to be involved in WSSV pathogenesis. ..
  2. Shulga N, Wilson Smith R, Pastorino J. Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent mechanism. Cell Cycle. 2009;8:3355-64 pubmed
    ..Notably, the detachment of hexokinase II from the mitochondria markedly potentiates the onset of caspase-2 induced mitochondrial damage, thus resulting in a synergistic induction of cisplatin induced cytotoxicity. ..
  3. Dahlhaus R, El Husseini A. Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome. Behav Brain Res. 2010;208:96-105 pubmed publisher
    ..These results provide for the first time evidence for an involvement of a neuroligin-neurexin protein network in core symptoms of FXS. ..
  4. Zorov D, Juhaszova M, Yaniv Y, Nuss H, Wang S, Sollott S. Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovasc Res. 2009;83:213-25 pubmed publisher
    ..This review provides an update on the current state of knowledge regarding the regulation of the mPTP...
  5. Yamamoto S, Ichishima K, Ehara T. Reduced volume-regulated outwardly rectifying anion channel activity in ventricular myocyte of type 1 diabetic mice. J Physiol Sci. 2009;59:87-96 pubmed publisher
    ..We postulate that an impairment PI3K-PIP3 pathway, which may be insulin-dependent, is responsible for the attenuation of VRAC currents in STZ-diabetic myocytes. ..
  6. Lee S, Hoang M, Han H, Kim H, Lee K, Kim K, et al. Pathogen inducible voltage-dependent anion channel (AtVDAC) isoforms are localized to mitochondria membrane in Arabidopsis. Mol Cells. 2009;27:321-7 pubmed publisher
    ..We also looked at the response of AtVDACs to biotic and abiotic stresses and found that four AtVDAC transcripts were rapidly up-regulated in response to a bacterial pathogen. ..
  7. Shoshan Barmatz V, De Pinto V, Zweckstetter M, Raviv Z, Keinan N, Arbel N. VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol Aspects Med. 2010;31:227-85 pubmed publisher
    ..This review also provides insight into the potential of VDAC1 as a rational target for new therapeutics. ..
  8. Hernández Carballo C, De Santiago Castillo J, Rosales Saavedra T, Perez Cornejo P, Arreola J. Control of volume-sensitive chloride channel inactivation by the coupled action of intracellular chloride and extracellular protons. Pflugers Arch. 2010;460:633-44 pubmed publisher
    ..The model depicts inactivation as a pore constriction that happens by simultaneous binding of H(+) and Cl(-) ions to the channel followed by a voltage-dependent conformational change that ultimately causes inactivation...
  9. Weber Lotfi F, Ibrahim N, Boesch P, Cosset A, Konstantinov Y, Lightowlers R, et al. Developing a genetic approach to investigate the mechanism of mitochondrial competence for DNA import. Biochim Biophys Acta. 2009;1787:320-7 pubmed publisher
    ..cerevisiae strains deleted for the VDAC-1 or VDAC-2 gene are severely compromised in DNA import. The prospect is now open to screen further mutant yeast strains to identify the elusive inner membrane DNA transporter. ..

More Information


  1. Liu B, Zhang W, Wang Z. Voltage-dependent anion channel in mammalian spermatozoa. Biochem Biophys Res Commun. 2010;397:633-6 pubmed publisher
    ..This review will discuss the presence, localization and function of VDAC in mammalian spermatozoa. ..
  2. Martin L, Gertz B, Pan Y, Price A, Molkentin J, Chang Q. The mitochondrial permeability transition pore in motor neurons: involvement in the pathobiology of ALS mice. Exp Neurol. 2009;218:333-46 pubmed publisher
    ..These results demonstrate that mitochondria have causal roles in the disease mechanisms in MNs in ALS mice. This work defines a new mitochondrial mechanism for MN degeneration in ALS. ..
  3. Martinez Caballero S, Dejean L, Kinnally M, Oh K, Mannella C, Kinnally K. Assembly of the mitochondrial apoptosis-induced channel, MAC. J Biol Chem. 2009;284:12235-45 pubmed publisher
    ..5-6 nm. The mitochondrial permeability data are inconsistent with formation of lipidic pores capable of transporting megadalton-sized macromolecules as observed with recombinant Bax in liposomes. ..
  4. Baines C. The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol. 2009;46:850-7 pubmed publisher
    ..The purpose of this review is to outline our current understanding of the molecular identity of the MPT pore and the many questions that still need to be answered. ..
  5. Galvita A, Grachev D, Azarashvili T, Baburina Y, Krestinina O, Stricker R, et al. The brain-specific protein, p42(IP4) (ADAP 1) is localized in mitochondria and involved in regulation of mitochondrial Ca2+. J Neurochem. 2009;109:1701-13 pubmed publisher
    ..Thus, we suggest that p42(IP4) is involved in the regulation of Ca(2+) transport in mitochondria. We propose that p42(IP4) promotes Ca(2+)-induced permeability transition pore opening and thus destabilizes mitochondria. ..
  6. Peixoto P, Ryu S, Kinnally K. Mitochondrial ion channels as therapeutic targets. FEBS Lett. 2010;584:2142-52 pubmed publisher
    ..This review is an update on both well established and putative mitochondrial channels regarding their composition, function, regulation, and therapeutic potential. ..
  7. Tikunov A, Johnson C, Pediaditakis P, Markevich N, MacDonald J, Lemasters J, et al. Closure of VDAC causes oxidative stress and accelerates the Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria. Arch Biochem Biophys. 2010;495:174-81 pubmed publisher
    ..of superoxide anions (O(2)(-)) from the intermembrane space (IMS) to the cytosol is mediated by voltage dependent anion channels (VDAC) in the outer membrane...
  8. Bay D, Court D. Effects of ergosterol on the structure and activity of Neurospora mitochondrial porin in liposomes. Can J Microbiol. 2009;55:1275-83 pubmed publisher
    ..Taken with other evidence for direct interactions of sterols with porins, these results support a link between these two molecules in mitochondrial membrane activity. ..
  9. Ozaki T, Yamashita T, Ishiguro S. Mitochondrial m-calpain plays a role in the release of truncated apoptosis-inducing factor from the mitochondria. Biochim Biophys Acta. 2009;1793:1848-59 pubmed publisher
    ..Our results demonstrated that mitochondrial m-calpain plays a role in the release of tAIF from mitochondria by cleaving VDAC, and tAIF is released through VDAC-Bax pores. ..
  10. Ferrer I. Altered mitochondria, energy metabolism, voltage-dependent anion channel, and lipid rafts converge to exhaust neurons in Alzheimer's disease. J Bioenerg Biomembr. 2009;41:425-31 pubmed publisher
    ..Cell exhaustion is suggested as being a determining element to interpret impaired neuron function, reduced molecular turnover, and enhanced cell death. ..
  11. Summers W, Court D. Origami in outer membrane mimetics: correlating the first detailed images of refolded VDAC with over 20 years of biochemical data. Biochem Cell Biol. 2010;88:425-38 pubmed publisher
  12. Tan W, Colombini M. VDAC closure increases calcium ion flux. Biochim Biophys Acta. 2007;1768:2510-5 pubmed
    ..These results are consistent with the view that VDAC closure is a pro-apoptotic signal. ..
  13. Best L, Brown P, Sener A, Malaisse W. Opposing effects of tenidap on the volume-regulated anion channel and K(ATP) channel activity in rat pancreatic beta-cells. Eur J Pharmacol. 2010;629:159-63 pubmed publisher
    ..These actions could at least in part explain the recently reported inhibitory actions of the drug on electrical and secretory activity in the beta-cell, and could also underlie other pharmacological actions of the drug. ..
  14. Mustacich D, Leonard S, Patel N, Traber M. Alpha-tocopherol beta-oxidation localized to rat liver mitochondria. Free Radic Biol Med. 2010;48:73-81 pubmed publisher
    ..An unexpected finding was that alpha-CEHC, the end product of alpha-tocopherol metabolism, was found almost exclusively in mitochondria. These data are the first to indicate a mitochondrial role in alpha-tocopherol metabolism...
  15. Scharstuhl A, Mutsaers H, Pennings S, Russel F, Wagener F. Involvement of VDAC, Bax and ceramides in the efflux of AIF from mitochondria during curcumin-induced apoptosis. PLoS ONE. 2009;4:e6688 pubmed publisher
    ..The composition of the AIF-releasing channel seems to be much more complex than previously thought. ..
  16. Jonas E. Molecular participants in mitochondrial cell death channel formation during neuronal ischemia. Exp Neurol. 2009;218:203-12 pubmed publisher
    ..The variety of possible molecular participants within the ion channel complex may be matched only by the variety of different types of programmed cell death. ..
  17. Crichton P, Parker N, Vidal Puig A, Brand M. Not all mitochondrial carrier proteins support permeability transition pore formation: no involvement of uncoupling protein 1. Biosci Rep. 2009;30:187-92 pubmed publisher
  18. Best L, Brown P, Yates A, Perret J, Virreira M, Beauwens R, et al. Contrasting effects of glycerol and urea transport on rat pancreatic beta-cell function. Cell Physiol Biochem. 2009;23:255-64 pubmed publisher
    ..This results in cell swelling, VRAC activation, electrical activity and insulin release. Glycerol appears to exert an additional effect, possibly related to its intracellular metabolism. ..
  19. Xiong Y, Ding H, Xu M, Gao J. Protective effects of asiatic acid on rotenone- or H2O2-induced injury in SH-SY5Y cells. Neurochem Res. 2009;34:746-54 pubmed publisher
    ..These data indicate that AA could protect neuronal cells against mitochondrial dysfunctional injury and suggest that AA might be developed as an agent for PD prevention or therapy. ..
  20. Cao L, Zhang X, Liu X, Chen T, Zhao M. Chloride channels and transporters in human corneal epithelium. Exp Eye Res. 2010;90:771-9 pubmed publisher
    ..Those molecules and their distribution may play important roles in maintaining resting Cl(-) fluxes and in regulating Cl(-) flux at corneal wounds, which may be a major contributor to wound electrical signaling...
  21. Dyrda A, Cytlak U, Ciuraszkiewicz A, Lipinska A, Cueff A, Bouyer G, et al. Local membrane deformations activate Ca2+-dependent K+ and anionic currents in intact human red blood cells. PLoS ONE. 2010;5:e9447 pubmed publisher
  22. Javadov S, Rajapurohitam V, Kilic A, Zeidan A, Choi A, Karmazyn M. Anti-hypertrophic effect of NHE-1 inhibition involves GSK-3beta-dependent attenuation of mitochondrial dysfunction. J Mol Cell Cardiol. 2009;46:998-1007 pubmed publisher
    ..In conclusion, anti-hypertrophic effect of NHE-1 inhibition can be mediated through activation of GSK-3beta which in turn induces inhibition of mPTP opening due to VDAC phosphorylation. ..
  23. Krestinina O, Grachev D, Odinokova I, Reiser G, Evtodienko Y, Azarashvili T. Effect of peripheral benzodiazepine receptor (PBR/TSPO) ligands on opening of Ca2+-induced pore and phosphorylation of 3.5-kDa polypeptide in rat brain mitochondria. Biochemistry (Mosc). 2009;74:421-9 pubmed
  24. Reina S, Palermo V, Guarnera A, Guarino F, Messina A, Mazzoni C, et al. Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell. FEBS Lett. 2010;584:2837-44 pubmed publisher
    ..This chimaera increased life span, indicating a more efficient bioenergetic metabolism and/or a better protection from ROS. ..
  25. Bertrand C, Zhang R, Pilewski J, Frizzell R. SLC26A9 is a constitutively active, CFTR-regulated anion conductance in human bronchial epithelia. J Gen Physiol. 2009;133:421-38 pubmed publisher
  26. Petrovic N, Walden T, Shabalina I, Timmons J, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adi. J Biol Chem. 2010;285:7153-64 pubmed publisher
  27. Alzualde A, Indakoetxea B, Ferrer I, Moreno F, Barandiaran M, Gorostidi A, et al. A novel PRNP Y218N mutation in Gerstmann-Sträussler-Scheinker disease with neurofibrillary degeneration. J Neuropathol Exp Neurol. 2010;69:789-800 pubmed publisher
    ..Genetic examination of the PRNP gene should be included in the workup of patients with poorly classifiable dementia. ..
  28. Prins J, Park S, Lurie D. Decreased expression of the voltage-dependent anion channel in differentiated PC-12 and SH-SY5Y cells following low-level Pb exposure. Toxicol Sci. 2010;113:169-76 pubmed publisher
    ..These results demonstrate that exposure to 5 and 10microM Pb reduces VDAC transcription and expression and is associated with reduced cellular ATP levels. ..
  29. Vincent A, Edwards J, McLean L, Hong Y, Cerri F, Lopez I, et al. Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy. Acta Neuropathol. 2010;120:477-89 pubmed publisher
    ..Our data suggest that an imbalance between mitochondrial biogenesis and fission may play a role in the pathogenesis of diabetic neuropathy. ..
  30. Baines C, Kaiser R, Sheiko T, Craigen W, Molkentin J. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol. 2007;9:550-5 pubmed
    ..These results indicate that Vdacs are dispensable for both MPT and Bcl-2 family member-driven cell death. ..
  31. Gonzalez Gronow M, Cuchacovich M, Francos R, Cuchacovich S, Fernandez M, Blanco A, et al. Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism. J Neuroimmunol. 2010;227:153-61 pubmed publisher
    ..Because VDAC and hexokinase-I are essential for brain protection from ischemic damage, the presence of these autoantibodies suggests a possible causal role in the neurologic pathogenesis of autism. ..
  32. Perevoshchikova I, Zorov S, Kotova E, Zorov D, Antonenko Y. Hexokinase inhibits flux of fluorescently labeled ATP through mitochondrial outer membrane porin. FEBS Lett. 2010;584:2397-402 pubmed publisher
    ..Therefore, the hexokinase-induced inhibition of the ATP flow mediated by VDAC was revealed in isolated mitochondria. ..
  33. Hiller S, Abramson J, Mannella C, Wagner G, Zeth K. The 3D structures of VDAC represent a native conformation. Trends Biochem Sci. 2010;35:514-21 pubmed publisher
    ..Furthermore, we validate the protein refolding approach and summarize the biochemical and biophysical evidence that links the 19-stranded structure to the native form of VDAC. ..
  34. Ichishima K, Yamamoto S, Iwamoto T, Ehara T. alpha-Adrenoceptor-mediated depletion of phosphatidylinositol 4, 5-bisphosphate inhibits activation of volume-regulated anion channels in mouse ventricular myocytes. Br J Pharmacol. 2010;161:193-206 pubmed publisher
    ..Our results indicate that the stimulation of alpha(1A)-adrenoceptors by PE inhibited the activation of cardiac VRAC current via PIP(3) depletion brought about by PLC-dependent reduction of membrane PIP(2) level. ..
  35. Danial N, Gimenez Cassina A, Tondera D. Homeostatic functions of BCL-2 proteins beyond apoptosis. Adv Exp Med Biol. 2010;687:1-32 pubmed
  36. De Pinto V, Messina A, Lane D, Lawen A. Voltage-dependent anion-selective channel (VDAC) in the plasma membrane. FEBS Lett. 2010;584:1793-9 pubmed publisher
    ..We discuss the possible biological function and relevance of VDAC in the plasma membrane and finally discuss a hypothetical model of how VDAC may be targeted to the plasma membrane. ..
  37. Salnikov V, Lukyanenko Y, Lederer W, Lukyanenko V. Distribution of ryanodine receptors in rat ventricular myocytes. J Muscle Res Cell Motil. 2009;30:161-70 pubmed publisher
    ..However, we did not find any evidence to support localization of RyRs to the mitochondrial inner membrane. ..
  38. Walther D, Bos M, Rapaport D, Tommassen J. The mitochondrial porin, VDAC, has retained the ability to be assembled in the bacterial outer membrane. Mol Biol Evol. 2010;27:887-95 pubmed publisher
    ..These results demonstrate that the basic mechanism of beta-barrel assembly in the OMs of bacteria and mitochondria is conserved. ..
  39. Yuqi L, Lei G, Yang L, Zongbin L, Hua X, Lin W, et al. Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation. BMC Med Genet. 2009;10:114 pubmed publisher
    ..We conclude that increased expression of mitochondrial VDAC and subcellular co-localization of VDAC/Bax increases mitochondrial permeability and apoptosis in cell lines carrying the mtDNA tRNAIle A4263G mutation. ..
  40. Varnier A, Kermarrec F, Blesneac I, Moreau C, Liguori L, Lenormand J, et al. A simple method for the reconstitution of membrane proteins into giant unilamellar vesicles. J Membr Biol. 2010;233:85-92 pubmed publisher
    ..This method is versatile since it is independent of the presence of the protein, as demonstrated by the fusion of fluorescently labeled submicron vesicles and proteoliposomes with GUVs. ..
  41. Stange A, Hedrich R, Roelfsema M. Ca(2+)-dependent activation of guard cell anion channels, triggered by hyperpolarization, is promoted by prolonged depolarization. Plant J. 2010;62:265-76 pubmed publisher
    ..Furthermore, prolonged depolarization to 0 mV alters the activity of Ca(2+) transport proteins, resulting in an overshoot of the cytosolic Ca(2+) level after returning the membrane potential to -100 mV. ..
  42. Weydert C, Cullen J. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc. 2010;5:51-66 pubmed publisher
    ..Other techniques including immunohistochemistry and immunogold can further evaluate the levels of the various antioxidant enzymes in tissues and cells. In general, these assays require 24-48 h to complete. ..
  43. Kusano T, Tateda C, Berberich T, Takahashi Y. Voltage-dependent anion channels: their roles in plant defense and cell death. Plant Cell Rep. 2009;28:1301-8 pubmed publisher
    ..In light of the current findings, we discuss the role of the PTP complex and VDAC as its component in plant pathogen defense and cell death. ..
  44. Yang Y, Lee C, Kuo C. Ionic flow enhances low-affinity binding: a revised mechanistic view into Mg2+ block of NMDA receptors. J Physiol. 2010;588:633-50 pubmed publisher
  45. Gutiérrez Aguilar M, Perez Martinez X, Chávez E, Uribe Carvajal S. In Saccharomyces cerevisiae, the phosphate carrier is a component of the mitochondrial unselective channel. Arch Biochem Biophys. 2010;494:184-91 pubmed publisher
    ..1 kDa PEG evidenced a higher sensitivity in mitochondria from the mutant strain. The above data suggest that the phosphate carrier is the phosphate sensor in YMUC and contributes to the structure of this channel. ..
  46. Ramírez C, Gonzalez M, Diaz M, Alonso R, Ferrer I, Santpere G, et al. VDAC and ERalpha interaction in caveolae from human cortex is altered in Alzheimer's disease. Mol Cell Neurosci. 2009;42:172-83 pubmed publisher
    ..Together with previous data in murine neurons demonstrating the participation of pl-VDAC in Abeta-induced neurotoxicity, these data suggest that the channel may be involved in membrane dysfunctioning observed in AD neuropathology. ..
  47. Singha U, Sharma S, Chaudhuri M. Downregulation of mitochondrial porin inhibits cell growth and alters respiratory phenotype in Trypanosoma brucei. Eukaryot Cell. 2009;8:1418-28 pubmed publisher
    ..We also found that the expressions of TAO and CP proteins are coordinately regulated in T. brucei according to mitochondrial energy demand...
  48. Zeth K, Thein M. Porins in prokaryotes and eukaryotes: common themes and variations. Biochem J. 2010;431:13-22 pubmed publisher
    ..Despite the lack of a clear evolutionary link between these protein families, their common principles and differences in assembly, architecture and function are summarized in the present review. ..
  49. Colombini M. The published 3D structure of the VDAC channel: native or not?. Trends Biochem Sci. 2009;34:382-9 pubmed publisher
    ..Here, I propose structural rearrangements that could occur spontaneously as a possible path to convert the 3D structure to my preferred biochemically determined native structure. ..
  50. Machado N, Baldeiras I, Pereira G, Pereira S, Oliveira P. Sub-chronic administration of doxorubicin to Wistar rats results in oxidative stress and unaltered apoptotic signaling in the lung. Chem Biol Interact. 2010;188:478-86 pubmed publisher
    ..The results obtained indicate for the first time that lungs from DOX-treated rats appear to be susceptible to increased lipid peroxidation, which can explain some cases of DOX-induced lung toxicity. ..