TCDB is operated by the Saier Lab Bioinformatics Group

1.B.8 The Mitochondrial and Plastid Porin (MPP) Family

Porins of the MPP family are found in eukaryotic organelles. The organelles include mitochondria of many eukaryotes as well as chloroplasts and plastids of plants. The best characterized members of the MPP family are the voltage-dependent anion-selective channel (VDAC) porins in the mitochondrial outer membrane. These porins have an estimated channel diameter of 2.5-3 nm. Topological models have been proposed in which VDAC consists of an N-terminal, globular α-helix and (1) 12 or 13 β-strands, (2) 16 β-strands or (3) 19 β-strands (now favored; see below) (Casadio et al., 2002). VDAC also appears to be present in plasma membranes (De Pinto et al., 2010). Prostacyclin receptor-mediated ATP release from ethrocytes requires VDAC (Sridharan et al., 2011).  Phylogenetic analyses of eukaryotic VDAC proteins from diverse organisms have been reported (Wojtkowska et al. 2012). Over-oxidation of cysteines and succinylation of cysteines in VDACs has been noticed (Saletti et al. 2018). Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase (Jahn et al. 2023).

A murine VDAC, VDAC-1, exhibits more than one topological type due to the use of alternative first exons. Thus, two different porins, differing only with respect to their N-termini, have been identified. One porin isoform (plasmalemmal VDAC-1) has a hydrophobic leader peptide that targets the protein through the golgi apparatus to the plasma membrane; the other isoform (mitochondrial VDAC-1) is translocated to the outer mitochondrial membrane because it lacks the N-terminal hydrophobic leader. The former is believed to account for the plasma membrane Maxi (large conductance) Cl- channel (Bahamonde et al., 2003).  Ca2+/Calmodulin-dependent protein kinase II disrupts the voltage dependency of VDAC in the mitochondrial membrane (Koren et al. 2023).

VDACs play a role in forming the mitochondrial permeability transition pore (PTP) which is important for Ca2+ homeostasis and programmed cell death. PTP is triggered by Ca2+ influx into mitochondria, and VDAC is permeable to Ca2+. It is also regulated by various compounds such as glutamate, NADH and nucleotides. VDAC has two nucleotide binding sites (Yehezkel et al., 2006). In VDAC1 the two cysteine residues seem not to be required for apoptosis or VDAC1 oligomerization (Aram et al., 2010).  Ions interact intimately with the inner walls of the channel and are selected by their 3-dimensional structure, not merely by their size and charge (Colombini 2016).  The N-terminus acts not as a gate on a stable barrel, but rather stabilizes the barrel, preventing its shift into a partially collapsed, low-conductance, closed state (Shuvo et al. 2016).

Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by loss of motor neurons. Misfolded mutant SOD1 binds directly to VDAC1. Direct binding of mutant SOD1 to VDAC1 inhibits conductance of channels when reconstituted in a lipid bilayer (Israelson et al., 2010). 

VDAC-protein interactions for each mammalian isoform (VDAC1, 2 and 3)  showed that VDAC1 is mainly involved in the maintenance of cellular homeostasis and in pro-apoptotic processes, whereas VDAC2 displays an anti-apoptotic role, while VDAC3 may contribute to mitochondrial protein quality control and act as a marker of oxidative status (Caterino et al. 2017). In pathological conditions, namely neurodegenerative and cardiovascular diseases, both VDAC1 and VDAC2 establish abnormal interactions aimed to counteract the mitochondrial dysfunction which contributes to end-organ damage.

Persistent opening of permeability transition pore,PTP, creates a bioenergetic crisis with collapse of the membrane potential, ATP depletion, Ca2+ deregulation, and release of proteins such as cytochrome c into the cytoplasm. These events promote cell death. The PTP traverses the inner and outer membranes and involves the ATP/ADP exchanger (ANT) in the inner membrane and VDAC in the other membrane (Cesura et al., 2003). A calcium-triggered conformational change of the mitochondrial phosphate carrier (PiC), facilitated by cyclophilin-D (CyP-D), may induce pore opening. This is enhanced by an association of the PiC with the 'c' conformation of the ANT. Agents that modulate pore opening may act on either or both the PiC and the ANT (Leung and Halestrap, 2008). Chitosan quaternary ammonium salts induce mitochondrial PTP opening (Xia et al. 2020).

The selective anti-tumour agent erastin causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. RNA-interference-mediated knockdown of VDAC2 or VDAC3 caused resistance to erastin. Using purified mitochondria expressing a single VDAC isoform, erastin alters the permeability of the outer mitochondrial membrane by binding directly to VDAC2. Thus, ligands to VDAC proteins can induce non-apoptotic cell death selectively in some tumour cells harbouring activating mutations in the RAS-RAF-MEK pathway (Yagoda et al., 2007).

VDACs form 19-stranded beta barrels with the first and last strand parallel. The hydrophobic outside perimeter of the barrel is covered by detergent molecules in a beltlike fashion (Hiller et al., 2010). In the presence of cholesterol, recombinant VDAC-1 can form voltage-gated channels in phospholipid bilayers similar to those of the native protein. The NMR measurements revealed the binding sites of VDAC-1 for the Bcl-2 protein, Bcl-x(L), for reduced beta-nicotinamide adenine dinucleotide, and for cholesterol. Bcl-x(L) interacts with the VDAC barrel laterally at strands 17 and 18 (Hiller et al., 2008). The position of the voltage-sensing N-terminal segment is oriented against the interior wall, causing a partial narrowing at the center of the pore. This segment is ideally positioned to regulate the conductance of ions and metabolites passing through the VDAC pore (Ujwal et al., 2008). 

Mitochondria import 90-99% of their proteins from the cytosol. Three protein families including Sam50, VDAC and Tom40 together with Mdm10 compose the set of integral beta-barrel proteins embedded in the mitochondrial outer membrane in S. cerevisiae (MOM) (Zeth 2010). The 16-stranded Sam50 protein forms part of the sorting and assembly machinery (SAM) and shows a clear evolutionary relationship to members of the bacterial Omp85 family (1.B.33). VDAC and Tom40 both adopt the same fold with 19 probable TMSs. Tom40 is in the TOM complex (3.A.8). Models of Tom40 and Sam50 have been developed using X-ray structures of related proteins. These models have been analyzed with respect to properties such as conservation and charge distribution yielding features related to their individual functions (Zeth 2010). 

The gene for VDAC1 in humans is over-expressed in many cancer types, and silencing of VDAC1 expression inhibits tumor development. Along with regulating cellular energy production and metabolism, VDAC1 is involved in the process of apoptosis by mediating the release of apoptotic proteins and interacting with anti-apoptotic proteins. The engagement of VDAC1 in the release of apoptotic proteins located in the inter-membranal space involves VDAC1 oligomerization that mediates the release of cytochrome c and AIF to the cytosol, subsequently leading to apoptotic cell death (Shoshan-Barmatz et al. 2015).

The mitochondrial permeability transition pore complex (PTPC) is involved in the control of the mitochondrial membrane permeabilization during apoptosis, necrosis and autophagy. Indeed, the adenine nucleotide translocator (ANT) and the voltage-dependent anion channel (VDAC), two major components of the PTPC, are the targets of a variety of proapoptotic inducers. Verrier et al. 2004 identified some of the interacting partners of ANT. During chemotherapy-induced apoptosis, some of these interactions were constant (e.g. ANT-VDAC), whereas others changed. Glutathione-S-transferase (GST) also interacts. This interaction is lost during apoptosis induction, suggesting that GST behaves as an endogenous repressor of PTPC and ANT pore opening. Thus, ANT is connected to mitochondrial proteins as well as to proteins from other organelles such as the endoplasmic reticulum, forming a dynamic polyprotein complex. Changes within this ANT interactome coordinate the lethal response of cells to apoptosis induction (Verrier et al. 2004).

Under cellular stress, human VDACs hetero-oligomerize and coaggregate with proteins that can form amyloidogenic and neurodegenerative deposits, implicating a role for VDACs in proteotoxicity. Gupta and Mahalakshmi 2019 mapped aggregation-prone regions of human VDACs, using isoform 3 as the model VDAC, and showed that the region comprising strands beta7-beta9 is aggregation prone. An alpha1-beta7-beta9 interaction (involving the hVDAC3 N-terminal alpha1 helix) can lower protein aggregation, whereas perturbations of this interaction promote VDAC aggregation. hVDAC3 aggregation proceeds via a partially unfolded structure.

VDACs 1 - 3, also called porins 1 - 3 or Por1-3) regulate the formation of the mitochondrial protein import gate in the OM, the translocase of the outer membrane (TOM) complex, and its dynamic exchange between the major form of a trimer and the minor form of a dimer (Endo and Sakaue 2019). The TOM complex dimer lacks the core subunit, Tom22, and mediates the import of a subset of mitochondrial proteins while the TOM complex trimer facilitates the import of most other mitochondrial proteins. Porins interact with both a translocating inner membrane (IM) protein like a carrier protein accumulated at the small TIM chaperones in the intermembrane space and the TIM22 complex, a downstream translocator in the IM for carrier protein import. Porins (VDACs) thereby facilitate the efficient transfer of carrier proteins to the IM during their import. Finally, porins facilitate the transfer of lipids between the OM and IM and promote a back-up pathway for cardiolipin synthesis in mitochondria. Thus, porins have roles in addition to metabolite transport in mitochondria (Endo and Sakaue 2019). Δpor1 cells lacking VDAC1 show enhanced phospholipid biosynthesis, accumulate lipid droplets, increase vacuoles and cell size, and overproduce and excrete inositol (Magrì et al. 2019).

Using human VDAC as a template scaffold, Srivastava and Mahalakshmi 2020 designed and engineered odd- and even-stranded structures of smaller (V2(16), V2(17), V2(18)) and larger (V2(20), V2(21)) barrel diameters. Determination of the structures, dynamics, and energetics of these engineered structures in bilayer membranes revealed that the 19-stranded barrel holds modest to low stability, but possesses superior voltage-gated channel regulation, efficient mitochondrial targeting and in vivo cell survival, with lipid-modulated stability, all of which supersede the occurrence of a metastable 19-stranded scaffold.

The VDAC porin regulates the formation of the mitochondrial protein import gate in the OM, the translocase of the outer membrane (TOM) complex, and its dynamic exchange between the major form of a trimer and the minor form of a dimer. The TOM complex dimer lacks a core subunit Tom22 and mediates the import of a subset of mitochondrial proteins while the TOM complex trimer facilitates the import of most other mitochondrial proteins (Endo and Sakaue 2019). Porin also interacts with both a translocating inner membrane (IM) protein like a carrier protein accumulated at the small TIM chaperones in the intermembrane space and the TIM22 complex, a downstream translocator in the IM for the carrier protein import. Porin thereby facilitates the efficient transfer of carrier proteins to the IM during their import. Finally, porin facilitates the transfer of lipids between the OM and IM and promotes a back-up pathway for the cardiolipin synthesis in mitochondria (Endo and Sakaue 2019).

VDAC provides the primary regulating pathway of water-soluble metabolites and ions across the mitochondrial outer membrane (Rostovtseva et al. 2021). VDAC responds to sufficiently large transmembrane potentials by transitioning to gated states in which ATP/ADP flux is reduced and calcium flux is increased. Two   cytosolic proteins, tubulin, and α-synuclein (αSyn), dock with VDAC by a mechanism in which the transmembrane potential draws their disordered, polyanionic C-terminal domains into and through the VDAC channel, thus physically blocking the pore. For both tubulin and αSyn, the blocked state is observed at much lower transmembrane potentials than VDAC gated states, such that in the presence of these cytosolic docking proteins, VDAC's sensitivity to transmembrane potential is dramatically increased. The features of the VDAC gated states relevant to reduced metabolite flux and increased calcium flux are preserved in the blocked state induced by either docking protein (Rostovtseva et al. 2021).

The generalized transport reaction catalyzed by VDACs is:

(Anionic) metabolites (out) ↔ anionic metabolites (intermembrane space)

References associated with 1.B.8 family:

Aiello R., A. Messina, B. Schiffler, R. Benz, G. Tasco, R. Casadio, V. De Pinto. (2004). Functional characterization of a second porin isoform in Drosophila melanogaster. DmPorin2 forms voltage-independent cation-selective pores. J Biol Chem. 279:25364-25373. 15054101
Alhozeel, B., S.K. Pandey, A. Shteinfer-Kuzmine, M. Santhanam, and V. Shoshan-Barmatz. (2024). Silencing the Mitochondrial Gatekeeper VDAC1 as a Potential Treatment for Bladder Cancer. Cells 13:. 38607066
Aram L., Geula S., Arbel N. and Shoshan-Barmatz V. (2010). VDAC1 cysteine residues: topology and function in channel activity and apoptosis. Biochem J. 427(3):445-54. 20192921
Austin, C.J., J. Kahlert, M. Kassiou, and L.M. Rendina. (2013). The translocator protein (TSPO): a novel target for cancer chemotherapy. Int J Biochem. Cell Biol. 45: 1212-1216. 23518318
Bahamonde, M.I., J.M. Fernández-Fernández, F.X. Guix, E. Vázquez, and M.A. Valverde. (2003). Plasma membrane voltage-dependent anion channel mediates antiestrogen-activated Maxi Cl- currents in C1300 neuroblastoma cells. J. Biol. Chem. 278: 33284-33289. 12794078
Bayrhuber, M., T. Meins, M. Habeck, S. Becker, K. Giller, S. Villinger, C. Vonrhein, C. Griesinger, M. Zweckstetter, and K. Zeth. (2008). Structure of the human voltage-dependent anion channel. Proc. Natl. Acad. Sci. USA 105: 15370-15375. 18832158
Bergdoll, L.A., M.T. Lerch, J.W. Patrick, K. Belardo, C. Altenbach, P. Bisignano, A. Laganowsky, M. Grabe, W.L. Hubbell, and J. Abramson. (2018). Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1. Proc. Natl. Acad. Sci. USA 115: E172-E179. 29279396
Blachly-Dyson, E., S. Peng, M. Colombini, and M. Forte. (1990). Selectivity changes in the site-directed mutants of the VDAC ion channel: structural implications. Science 247: 1233-1236. 1690454
Buettner, R., G. Papoutsoglou, E. Scemes, D.C. Spray, and R. Dermietzel. (2000). Evidence for secretory pathway localization of a voltage-dependent anion channel isoform. Proc. Natl. Acad. Sci. USA 97: 3201-3206. 10716730
Casadio, R., I. Jacoboni, A. Messina, and V. De Pinto. (2002). A 3D model of the voltage-dependent anion channel (VDAC). FEBS Lett. 520: 1-7. 12044860
Caterino, M., M. Ruoppolo, A. Mandola, M. Costanzo, S. Orrù, and E. Imperlini. (2017). Protein-protein interaction networks as a new perspective to evaluate distinct functional roles of voltage-dependent anion channel isoforms. Mol Biosyst 13: 2466-2476. 29028058
Cesura, A.M., E. Pinard, R. Schubenel, V. Goetschy, A. Friedlein, H. Langen, P. Polcic, M.A. Forte, P. Bernardi, and J.A. Kemp. (2003). The voltage-dependent anion channel is the target for a new class of inhibitors of the mitochondrial permeability transition pore. J. Biol. Chem. 278: 49812-49818. 12952973
Checchetto, V., S. Reina, A. Magrì, I. Szabo, and V. De Pinto. (2014). Recombinant Human Voltage Dependent Anion Selective Channel Isoform 3 (hVDAC3) Forms Pores with a Very Small Conductance. Cell Physiol Biochem 34: 842-853. 25171321
Colombini, M. (2016). The VDAC channel: Molecular basis for selectivity. Biochim. Biophys. Acta. [Epub: Ahead of Print] 26826035
Craigen, W.J. and B.H. Graham. (2008). Genetic strategies for dissecting mammalian and Drosophila voltage-dependent anion channel functions. J. Bioenerg. Biomembr. 40: 207-212. 18622693
De Pinto, V., A. Messina, D.J. Lane, and A. Lawen. (2010). Voltage-dependent anion-selective channel (VDAC) in the plasma membrane. FEBS Lett. 584: 1793-1799. 20184885
De Pinto, V., R. Benz, C. Caggese, and F. Palmieri. (1989). Characterization of the mitochondrial porin from Drosophila melanogaster. Biochim. Biophys. Acta. 987: 1-7. 2480813
Eddy, M.T., T.Y. Yu, G. Wagner, and R.G. Griffin. (2019). Structural characterization of the human membrane protein VDAC2 in lipid bilayers by MAS NMR. J Biomol NMR 73: 451-460. 31407201
Ellenrieder, L., M.P. Dieterle, K.N. Doan, C.U. Mårtensson, A. Floerchinger, M.L. Campo, N. Pfanner, and T. Becker. (2019). Dual Role of Mitochondrial Porin in Metabolite Transport across the Outer Membrane and Protein Transfer to the Inner Membrane. Mol. Cell 73: 1056-1065.e7. 30738704
Endo, T. and H. Sakaue. (2019). Multifaceted roles of porin in mitochondrial protein and lipid transport. Biochem Soc Trans 47: 1269-1277. 31670371
Fischer, K., A. Weber, S. Brink, B. Arbinger, D. Schünemann, S. Borchert, H.W. Heldt, B. Popp, R. Benz, T.A. Link, C. Eckerskorn, and U.-I. Flügge. (1994). Porins from plants: molecular cloning and functional characterization of two new members of the porin family. J. Biol. Chem. 269: 25754-25760. 7523392
Flinner, N., L. Ellenrieder, S.B. Stiller, T. Becker, E. Schleiff, and O. Mirus. (2013). Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex. Biochim. Biophys. Acta. 1833: 3314-3325. 24135058
Godbole, A., R. Mitra, A.K. Dubey, P.S. Reddy, and M.K. Mathew. (2011). Bacterial expression, purification and characterization of a rice voltage-dependent, anion-selective channel isoform, OsVDAC4. J. Membr. Biol. 244: 67-80. 22057934
Graham, B.H., Z. Li, E.P. Alesii, P. Versteken, C. Lee, J. Wang, and W.J. Craigen. (2010). Neurologic dysfunction and male infertility in Drosophila porin mutants: a new model for mitochondrial dysfunction and disease. J. Biol. Chem. 285: 11143-11153. 20110367
Guardiani, C., A. Magrì, A. Karachitos, M.C. Di Rosa, S. Reina, I. Bodrenko, A. Messina, H. Kmita, M. Ceccarelli, and V. De Pinto. (2018). yVDAC2, the second mitochondrial porin isoform of Saccharomyces cerevisiae. Biochim. Biophys. Acta. 1859: 270-279. 29408701
Guarino, F., V. Specchia, G. Zapparoli, A. Messina, R. Aiello, M.P. Bozzetti, and V. De Pinto. (2006). Expression and localization in spermatozoa of the mitochondrial porin isoform 2 in Drosophila melanogaster. Biochem. Biophys. Res. Commun. 346: 665-670. 16774740
Gupta, A. and R. Mahalakshmi. (2019). Helix-strand interaction regulates stability and aggregation of the human mitochondrial membrane protein channel VDAC3. J Gen Physiol. [Epub: Ahead of Print] 30674561
Häusler, E., K. Fredriksson, I. Goba, C. Peters, K. Raltchev, L. Sperl, A. Steiner, S. Weinkauf, and F. Hagn. (2020). Quantifying the insertion of membrane proteins into lipid bilayer nanodiscs using a fusion protein strategy. Biochim. Biophys. Acta. Biomembr 1862: 183190. 31935366
Hiller, S., J. Abramson, C. Mannella, G. Wagner, and K. Zeth. (2010). The 3D structures of VDAC represent a native conformation. Trends. Biochem. Sci. 35: 514-521. 20708406
Hiller, S., R.G. Garces, T.J. Malia, V.Y. Orekhov, M. Colombini, and G. Wagner. (2008). Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 321: 1206-1210. 18755977
Israelson, A., N. Arbel, S. Da Cruz, H. Ilieva, K. Yamanaka, V. Shoshan-Barmatz, and D.W. Cleveland. (2010). Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of inherited ALS. Neuron. 67: 575-587. 20797535
Jahn, H., L. Bartoš, G.I. Dearden, J.S. Dittman, J.C.M. Holthuis, R. Vácha, and A.K. Menon. (2023). Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase. Nat Commun 14: 8115. 38065946
Jeanteur, D., J.H. Lakey, and F. Pattus. (1991). The bacterial porin superfamily: sequence alignment and structure prediction. Mol. Microbiol. 5: 2153-2164. 1662760
Jeanteur, D., J.H. Lakey, and F. Pattus. (1994). The porin superfamily: diversity and common features. In Bacterial Cell Wall, J.M. Ghuysen and R. Hakenbeck (Eds.), Amsterdam, Elsevier, pp. 363-380.
Kanwar, P., H. Samtani, S.K. Sanyal, A.K. Srivastava, P. Suprasanna, and G.K. Pandey. (2020). VDAC and its interacting partners in plant and animal systems: an overview. Crit Rev Biotechnol 40: 715-732. 32338074
Klinger, A., V. Gosch, U. Bodensohn, R. Ladig, and E. Schleiff. (2019). The signal distinguishing between targeting of outer membrane β-barrel protein to plastids and mitochondria in plants. Biochim. Biophys. Acta. Mol. Cell Res 1866: 663-672. 30633951
Kojima, S., M. Iwamoto, S. Oiki, S. Tochigi, and H. Takahashi. (2018). Thylakoid membranes contain a non-selective channel permeable to small organic molecules. J. Biol. Chem. 293: 7777-7785. 29602906
Koren, D.T., R. Shrivastava, and S. Ghosh. (2023). Ca/Calmodulin-Dependent Protein Kinase II Disrupts the Voltage Dependency of the Voltage-Dependent Anion Channel on the Lipid Bilayer Membrane. J Phys Chem B. [Epub: Ahead of Print] 37040575
Lawen, A., J.D. Ly, D.J. Lane, K. Zarschler, A. Messina, and V. De Pinto. (2005). Voltage-dependent anion-selective channel 1 (VDAC1)--a mitochondrial protein, rediscovered as a novel enzyme in the plasma membrane. Int J Biochem. Cell Biol. 37: 277-282. 15474974
Leung, A.W. and A.P. Halestrap. Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore. Biochim. Biophys. Acta. 1777: 946-952. 18407825
Ludwig, O., R. Benz, and J.E. Schultz. (1989). Porin of Paramecium mitochondria isolation, characterization and ion selectivity of the closed state. Biochim. Biophys. Acta. 978: 319-327. 2536559
Magrì, A., M.C. Di Rosa, I. Orlandi, F. Guarino, S. Reina, M. Guarnaccia, G. Morello, A. Spampinato, S. Cavallaro, A. Messina, M. Vai, and V. De Pinto. (2019). Deletion of Voltage-Dependent Anion Channel 1 knocks mitochondria down triggering metabolic rewiring in yeast. Cell Mol Life Sci. [Epub: Ahead of Print] 31655859
Makiuchi, T., F. Mi-ichi, K. Nakada-Tsukui, and T. Nozaki. (2013). Novel TPR-containing subunit of TOM complex functions as cytosolic receptor for Entamoeba mitosomal transport. Sci Rep 3: 1129. 23350036
Makki, A., P. Rada, V. Žárský, S. Kereïche, L. Kováčik, M. Novotný, T. Jores, D. Rapaport, and J. Tachezy. (2019). Triplet-pore structure of a highly divergent TOM complex of hydrogenosomes in Trichomonas vaginalis. PLoS Biol 17: e3000098. 30608924
Mannella, C. (2023). In Silico Exploration of Alternative Conformational States of VDAC. Molecules 28:. 37110543
Martinez-Arguelles, D.B., J.W. Nedow, H.J. Gukasyan, and V. Papadopoulos. (2022). Oral administration of VDAC1-derived small molecule peptides increases circulating testosterone levels in male rats. Front Endocrinol (Lausanne) 13: 1003017. 36686419
Maurya, S.R. and R. Mahalakshmi. (2014). Cysteine Residues Impact the Stability and Micelle Interaction Dynamics of the Human Mitochondrial β-Barrel Anion Channel hVDAC-2. PLoS One 9: e92183. 24642864
Maurya, S.R. and R. Mahalakshmi. (2014). Influence of protein-micelle ratios and cysteine residues on the kinetic stability and unfolding rates of human mitochondrial VDAC-2. PLoS One 9: e87701. 24494036
Maurya, S.R. and R. Mahalakshmi. (2015). VDAC-2: Mitochondrial outer membrane regulator masquerading as a channel? FEBS J. [Epub: Ahead of Print] 26709731
Messina, A., S. Reina, F. Guarino, and V. De Pinto. (2012). VDAC isoforms in mammals. Biochim. Biophys. Acta. 1818: 1466-1476. 22020053
Miyata, N., S. Fujii, and O. Kuge. (2018). Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast. J. Biol. Chem. [Epub: Ahead of Print] 30237174
Naghdi, S., P. Várnai, and G. Hajnóczky. (2015). Motifs of VDAC2 required for mitochondrial Bak import and tBid-induced apoptosis. Proc. Natl. Acad. Sci. USA 112: E5590-5599. 26417093
Ngo, V.A., M. Queralt-Martín, F. Khan, L. Bergdoll, J. Abramson, S.M. Bezrukov, T.K. Rostovtseva, D.P. Hoogerheide, and S.Y. Noskov. (2022). The Single Residue K12 Governs the Exceptional Voltage Sensitivity of Mitochondrial Voltage-Dependent Anion Channel Gating. J. Am. Chem. Soc. 144: 14564-14577. 35925797
Nikaido, H. (1992). Porins and specific channels of bacterial outer membranes. Mol. Microbiol. 6: 435-442. 1373213
Pan, X., Z. Chen, X. Yang, and G. Liu. (2014). Arabidopsis Voltage-Dependent Anion Channel 1 (AtVDAC1) Is Required for Female Development and Maintenance of Mitochondrial Functions Related to Energy-Transaction. PLoS One 9: e106941. 25192453
Pittalà, M.G.G., S. Reina, S.C. Nibali, A. Cucina, S.A.M. Cubisino, V. Cunsolo, G.F. Amodeo, S. Foti, V. De Pinto, R. Saletti, and A. Messina. (2022). Specific Post-Translational Modifications of VDAC3 in ALS-SOD1 Model Cells Identified by High-Resolution Mass Spectrometry. Int J Mol Sci 23:. 36555496
Preto, J., H. Gorny, and I. Krimm. (2022). A Deep Dive into VDAC1 Conformational Diversity Using All-Atom Simulations Provides New Insights into the Structural Origin of the Closed States. Int J Mol Sci 23:. 35163095
Puurand, M., K. Tepp, N. Timohhina, J. Aid, I. Shevchuk, V. Chekulayev, and T. Kaambre. (2019). Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease. Cells 8:. 30871176
Ramos, S.V., M.C. Hughes, and C.G.R. Perry. (2019). Altered skeletal muscle microtubule-mitochondrial VDAC2 binding is related to bioenergetic impairments after paclitaxel but not vinblastine chemotherapies. Am. J. Physiol. Cell Physiol. 316: C449-C455. 30624982
Rauch, G. and O. Moran. (1994). On the structure of mitochondrial porins and its homologies with bacterial porins. Biochem. Biophys. Res. Commun. 200: 908-915. 8179626
Reina, S., V. Checchetto, R. Saletti, A. Gupta, D. Chaturvedi, C. Guardiani, F. Guarino, M.A. Scorciapino, A. Magrì, S. Foti, M. Ceccarelli, A.A. Messina, R. Mahalakshmi, I. Szabo, and V. De Pinto. (2016). VDAC3 as a sensor of oxidative state of the intermembrane space of mitochondria: the putative role of cysteine residue modifications. Oncotarget 7: 2249-2268. 26760765
Röhl, T., M. Motzkus, and J. Soll. (1999). The outer envelope protein OEP24 from pea chloroplasts can functionally replace the mitochondrial VDAC in yeast. FEBS Lett. 460: 491-494. 10556523
Roosens, N., F. Al Bitar, M. Jacobs, and F. Homblé. (2000). Characterization of a cDNA encoding a rice mitochondrial voltage-dependent anion channel and its gene expression studied upon plant development and osmotic stress. Biochim. Biophys. Acta 1463: 470-476. 10675523
Rostovtseva, T.K., S.M. Bezrukov, and D.P. Hoogerheide. (2021). Regulation of Mitochondrial Respiration by VDAC Is Enhanced by Membrane-Bound Inhibitors with Disordered Polyanionic C-Terminal Domains. Int J Mol Sci 22:. 34298976
Saletti, R., S. Reina, M.G.G. Pittalà, A. Magrì, V. Cunsolo, S. Foti, and V. De Pinto. (2018). Post-translational modifications of VDAC1 and VDAC2 cysteines from rat liver mitochondria. Biochim. Biophys. Acta. [Epub: Ahead of Print] 29890122
Salimi, A., S. Atashbar, and M. Shabani. (2021). Gallic acid inhibits celecoxib-induced mitochondrial permeability transition and reduces its toxicity in isolated cardiomyocytes and mitochondria. Hum Exp Toxicol 40: S530-S539. 34715756
Santos, H.J., K. Imai, Y. Hanadate, Y. Fukasawa, T. Oda, F. Mi-Ichi, and T. Nozaki. (2016). Screening and discovery of lineage-specific mitosomal membrane proteins in Entamoeba histolytica. Mol Biochem Parasitol 209: 10-17. 26792249
Sbidian E., Eftekahri P., Viguier M., Laroche L., Chosidow O., Gosselin P., Trouche F., Bonnet N., Arfi C., Tubach F. and Bachelez H. (201). National survey of psoriasis flares after 2009 monovalent H1N1/seasonal vaccines. Dermatology. 229(2):130-5. 25171322
Schulz, G.E. (1996). Porins: general to specific, native to engineered passive pores. Curr. Opin. Struc. Biol. 6: 485-490. 8794162
Shares, B.H., C.O. Smith, T.J. Sheu, R. Sautchuk, Jr, K. Schilling, L.C. Shum, A. Paine, A. Huber, E. Gira, E. Brown, H. Awad, and R.A. Eliseev. (2020). Inhibition of the mitochondrial permeability transition improves bone fracture repair. Bone 137: 115391. 32360587
Shoshan-Barmatz, V., D. Ben-Hail, L. Admoni, Y. Krelin, and S.S. Tripathi. (2015). The mitochondrial voltage-dependent anion channel 1 in tumor cells. Biochim. Biophys. Acta. 1848: 2547-2575. 25448878
Shoshan-Barmatz, V., E. Nahon-Crystal, A. Shteinfer-Kuzmine, and R. Gupta. (2018). VDAC1, mitochondrial dysfunction, and Alzheimer''s disease. Pharmacol Res 131: 87-101. [Epub: Ahead of Print] 29551631
Shoshan-Barmatz, V., Y. Krelin, A. Shteinfer-Kuzmine, and T. Arif. (2017). Voltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics. Front Oncol 7: 154. 28824871
Shuvo, S.R., F.G. Ferens, and D.A. Court. (2016). The N-terminus of VDAC: Structure, mutational analysis, and a potential role in regulating barrel shape. Biochim. Biophys. Acta. [Epub: Ahead of Print] 26997586
Shuvo, S.R., L.M. Wiens, S. Subramaniam, J.R. Treberg, and D.A. Court. (2019). Increased reactive oxygen species production and maintenance of membrane potential in VDAC-less Neurospora crassa mitochondria. J. Bioenerg. Biomembr. 51: 341-354. 31392584
Song, J., C. Midson, E. Blachly-Dyson, M. Forte, and M. Colombini. (1998). The topology of VDAC as probed by biotin modification. J. Biol. Chem. 273: 24406-24413. 9733730
Specchia, V., F. Guarino, A. Messina, M.P. Bozzetti, and V. De Pinto. (2008). Porin isoform 2 has a different localization in Drosophila melanogaster ovaries than porin 1. J. Bioenerg. Biomembr. 40: 219-226. 18686020
Sridharan M., Bowles EA., Richards JP., Krantic M., Davis KL., Dietrich KA., Stephenson AH., Ellsworth ML. and Sprague RS. (2012). Prostacyclin receptor-mediated ATP release from erythrocytes requires the voltage-dependent anion channel. Am J Physiol Heart Circ Physiol. 302(3):H553-9. 22159995
Srivastava, S.R. and R. Mahalakshmi. (2020). Evolutionary selection of a 19-stranded mitochondrial β-barrel scaffold bears structural and functional significance. J. Biol. Chem. [Epub: Ahead of Print] 32817169
Srivastava, S.R., P. Zadafiya, and R. Mahalakshmi. (2018). Hydrophobic Mismatch Modulates Stability and Plasticity of Human Mitochondrial VDAC2. Biophys. J. [Epub: Ahead of Print] 30503532
Teixeira, J., C. Oliveira, F. Cagide, R. Amorim, J. Garrido, F. Borges, and P.J. Oliveira. (2018). Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid. J Enzyme Inhib Med Chem 33: 567-576. 29513043
Troll, H., D. Malchow, A. Müller-Taubenberger, B. Humbel, F. Lottspeich, M. Ecke, G. Gerisch, A. Schmid, and R. Benz. (1992). Purification, functional characterization, and cDNA sequencing of mitochondrial porin from Dictyostelium discoideum. J. Biol. Chem. 267: 21072-21079. 1328220
Ujwal, R., D. Cascio, J.P. Colletier, S. Faham, J. Zhang, L. Toro, P. Ping, and J. Abramson. (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. 18988731
Unten, Y., M. Murai, T. Yamamoto, A. Watanabe, N. Ichimaru, S. Aburaya, W. Aoki, Y. Shinohara, and H. Miyoshi. (2019). Pentenediol-Type Compounds Specifically Bind to Voltage-Dependent Anion Channel 1 in Saccharomyces cerevisiae Mitochondria. Biochemistry 58: 1141-1154. 30657320
Ventura, C., M. Junco, F.X. Santiago Valtierra, M. Gooz, Y. Zhiwei, D.M. Townsend, P.M. Woster, and E.N. Maldonado. (2023). Synergism of small molecules targeting VDAC with sorafenib, regorafenib or lenvatinib on hepatocarcinoma cell proliferation and survival. Eur J Pharmacol 957: 176034. 37652292
Verrier, F., A. Deniaud, M. Lebras, D. Métivier, G. Kroemer, B. Mignotte, G. Jan, and C. Brenner. (2004). Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis. Oncogene 23: 8049-8064. 15377997
Wojtkowska, M., M. Jąkalski, J.R. Pieńkowska, O. Stobienia, A. Karachitos, T.M. Przytycka, J. Weiner, 3rd, H. Kmita, and W. Makałowski. (2012). Phylogenetic analysis of mitochondrial outer membrane β-barrel channels. Genome Biol Evol 4: 110-125. 22155732
Wunderlich, J. (2022). Updated List of Transport Proteins in. Front Cell Infect Microbiol 12: 926541. 35811673
Xia, C., B. Fu, X. Zhang, C. Qin, and J.C. Jin. (2020). Chitosan quaternary ammonium salt induced mitochondrial membrane permeability transition pore opening study in a spectroscopic perspective. Int J Biol Macromol 165: 314-320. [Epub: Ahead of Print] 32987072
Yagoda N., M. von Rechenberg, E. Zaganjor, A.J. Bauer, W.S. Yang, D.J. Fridman, A.J. Wolpaw, I. Smukste, J.M. Peltier, J.J. Boniface, R. SmitH, S.L. Lessnick, S. Sahasrabudhe, B.R. Stockwell. (2007). RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 447: 864-868 17568748
Yehezkel, G., Hadad, N., Zaid, H., Sivan, S., and Shoshan-Barmatz, V. (2006). Nucleotide-binding sites in the voltage-dependent anion channel: characterization and localization. J. Biol. Chem. 281: 5938-5946. 16354668
Zeth, K. (2010). Structure and evolution of mitochondrial outer membrane proteins of β-barrel topology. Biochim. Biophys. Acta. 1797: 1292-1299. 20450883
Zhang, E., I. Mohammed Al-Amily, S. Mohammed, C. Luan, O. Asplund, M. Ahmed, Y. Ye, D. Ben-Hail, A. Soni, N. Vishnu, P. Bompada, Y. De Marinis, L. Groop, V. Shoshan-Barmatz, E. Renström, C.B. Wollheim, and A. Salehi. (2018). Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells. Cell Metab. [Epub: Ahead of Print] 30293774
Zhang, J., L. Liu, Y. Li, Y. Huang, S. Xiao, Z. Deng, Z. Zheng, J. Li, M. Liang, G. Xie, X. Chen, Y. Deng, W. Tan, H. Su, G. Wu, C. Cai, X. Chen, and F. Zou. (2023). HSP90 C-terminal domain inhibition promotes VDAC1 oligomerization via decreasing K274 mono-ubiquitination in Hepatocellular Carcinoma. Neoplasia 44: 100935. 37717471