VDAC1

Voltage-dependent anion channel 1

Rendering based on PDB 2JK4​.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols VDAC1 ; PORIN; VDAC-1
External IDs OMIM: 604492 MGI: 106919 HomoloGene: 107244 GeneCards: VDAC1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 7416 22333
Ensembl ENSG00000213585 ENSMUSG00000020402
UniProt P21796 Q60932
RefSeq (mRNA) NM_003374 NM_011694
RefSeq (protein) NP_003365 NP_035824
Location (UCSC) Chr 5:
133.97 – 134.01 Mb		 Chr 11:
52.36 – 52.39 Mb
PubMed search

Voltage-dependent anion-selective channel protein 1 is a protein that in humans is encoded by the VDAC1 gene on chromosome 5.[1][2] This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms, which are involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis.[3][4][5][6] In particular, VDAC1 is the major calcium ion transport channel and is implicated in cancer and Parkinson’s Disease (PD).[7][8]

Structure

The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore.[9] For VDAC1, this barrel-like channel is composed of 19 amphipathic β-strands, and the end of the N-terminal contains α-helix segments. The N-terminal is proposed to as a gate to the pore via swinging motions facilitated by a short glycine-containing motif. Additionally, the N-terminal serves as a docking site for HK1 binding.[10]

Function

VDAC1 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms.[11] Of the three isoforms, VDAC1 is the main calcium ion transport channel and the most abundantly transcribed.[8][12] VDACs are involved in cell metabolism by transporting ATP and other small metabolites across the outer mitochondrial membrane (OMM). Of note, its role in transporting calcium ions allows the protein to regulate the TCA cycle and, by extension, reactive oxygen species (ROS) production.[7] In yeast cells, ROS accumulates in response to oxidative stress, which results in impaired mitochondrial function and a “petite” phenotype. However, petite yeast cells exhibit a longer lifespan than wildtype cells and indicate a protective function by VDAC1 in similar circumstances, such as aging.[10][12] In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis. VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP.[11]

Clinical Significance

VDAC1 has been implicated in cancer through its interactions with antiapoptotic Bcl-2 proteins, particularly Bcl-xl, and Mcl-1, which are overexpressed during cancer. These two Bcl-2 proteins interact with VDAC1 to regulate calcium ion transport across the OMM and, ultimately, ROS production. While high levels of ROS induce cell death, non-lethal levels interfere with signal transduction pathways that can then promote cell proliferation, migration, and invasion in cancer cells.[7] Moreover, VDAC1 overexpression has been associated with increased apoptotic response and anti-cancer drugs and treatment efficacy, further supporting VDAC1 as a therapeutic target for cancer treatment.[7][13]

VDAC1 function in calcium ion transport also involves the protein in neurodegenerative diseases. In PD, VDAC1 increases calcium ion levels within the mitochondria, resulting in increased mitochondrial permeability, disrupted mitochondrial membrane potential, elevated ROS production, cell death, and neuronal degeneration.[8]

Interactions

VDAC1 has been shown to interact with:

See also

References

  1. ↑ Blachly-Dyson E, Baldini A, Litt M, McCabe ER, Forte M (July 1994). "Human genes encoding the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane: mapping and identification of two new isoforms". Genomics 20 (1): 62–7. doi:10.1006/geno.1994.1127. PMID 7517385.
  2. ↑ "Entrez Gene: VDAC1 voltage-dependent anion channel 1".
  3. ↑ Subedi KP, Kim JC, Kang M, Son MJ, Kim YS, Woo SH (Feb 2011). "Voltage-dependent anion channel 2 modulates resting Ca²+ sparks, but not action potential-induced Ca²+ signaling in cardiac myocytes". Cell Calcium 49 (2): 136–43. doi:10.1016/j.ceca.2010.12.004. PMID 21241999.
  4. 1 2 Alvira CM, Umesh A, Husted C, Ying L, Hou Y, Lyu SC, Nowak J, Cornfield DN (Nov 2012). "Voltage-dependent anion channel-2 interaction with nitric oxide synthase enhances pulmonary artery endothelial cell nitric oxide production". American Journal of Respiratory Cell and Molecular Biology 47 (5): 669–78. doi:10.1165/rcmb.2011-0436OC. PMID 22842492.
  5. ↑ Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (Jul 2003). "VDAC2 inhibits BAK activation and mitochondrial apoptosis". Science 301 (5632): 513–7. doi:10.1126/science.1083995. PMID 12881569.
  6. ↑ Li Z, Wang Y, Xue Y, Li X, Cao H, Zheng SJ (Feb 2012). "Critical role for voltage-dependent anion channel 2 in infectious bursal disease virus-induced apoptosis in host cells via interaction with VP5". Journal of Virology 86 (3): 1328–38. doi:10.1128/JVI.06104-11. PMID 22114330.
  7. 1 2 3 4 5 Huang H, Shah K, Bradbury NA, Li C, White C (23 October 2014). "Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation". Cell Death & Disease 5: e1482. doi:10.1038/cddis.2014.419. PMID 25341036.
  8. 1 2 3 Chu Y, Goldman JG, Kelly L, He Y, Waliczek T, Kordower JH (Sep 2014). "Abnormal alpha-synuclein reduces nigral voltage-dependent anion channel 1 in sporadic and experimental Parkinson's disease". Neurobiology of Disease 69: 1–14. doi:10.1016/j.nbd.2014.05.003. PMID 24825319.
  9. ↑ Amodeo GF, Scorciapino MA, Messina A, De Pinto V, Ceccarelli M (2014). "Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel". PLOS ONE 9 (8): e103879. doi:10.1371/journal.pone.0103879. PMID 25084457.
  10. 1 2 3 Reina S, Palermo V, Guarnera A, Guarino F, Messina A, Mazzoni C, De Pinto V (Jul 2010). "Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell". FEBS Letters 584 (13): 2837–44. doi:10.1016/j.febslet.2010.04.066. PMID 20434446.
  11. 1 2 Lee MJ, Kim JY, Suk K, Park JH (May 2004). "Identification of the hypoxia-inducible factor 1 alpha-responsive HGTD-P gene as a mediator in the mitochondrial apoptotic pathway". Molecular and Cellular Biology 24 (9): 3918–27. doi:10.1128/mcb.24.9.3918-3927.2004. PMID 15082785.
  12. 1 2 De Pinto V, Guarino F, Guarnera A, Messina A, Reina S, Tomasello FM, Palermo V, Mazzoni C (2010). "Characterization of human VDAC isoforms: a peculiar function for VDAC3?". Biochimica et Biophysica Acta 1797 (6-7): 1268–75. doi:10.1016/j.bbabio.2010.01.031. PMID 20138821.
  13. 1 2 Weisthal S, Keinan N, Ben-Hail D, Arif T, Shoshan-Barmatz V (Oct 2014). "Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction". Biochimica et Biophysica Acta 1843 (10): 2270–81. doi:10.1016/j.bbamcr.2014.03.021. PMID 24704533.
  14. 1 2 Weng C, Li Y, Xu D, Shi Y, Tang H (March 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem. 280 (11): 10491–500. doi:10.1074/jbc.M412819200. PMID 15637055.
  15. 1 2 Shi Y, Chen J, Weng C, Chen R, Zheng Y, Chen Q, Tang H (June 2003). "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. Biophys. Res. Commun. 305 (4): 989–96. doi:10.1016/s0006-291x(03)00871-4. PMID 12767928.
  16. ↑ Shimizu S, Konishi A, Kodama T, Tsujimoto Y (March 2000). "BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3100–5. doi:10.1073/pnas.97.7.3100. PMC: 16199. PMID 10737788.
  17. ↑ Shimizu S, Narita M, Tsujimoto Y (June 1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC". Nature 399 (6735): 483–7. doi:10.1038/20959. PMID 10365962.
  18. ↑ Schwarzer C, Barnikol-Watanabe S, Thinnes FP, Hilschmann N (September 2002). "Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74". Int. J. Biochem. Cell Biol. 34 (9): 1059–70. doi:10.1016/s1357-2725(02)00026-2. PMID 12009301.
  19. ↑ Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y (October 2000). "Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC". Oncogene 19 (42): 4807–14. doi:10.1038/sj.onc.1203868. PMID 11039896.
  20. ↑ Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (May 2003). "Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria". Circ. Res. 92 (8): 873–80. doi:10.1161/01.RES.0000069215.36389.8D. PMC: 3691672. PMID 12663490.
  21. ↑ Sun Y, Vashisht AA, Tchieu J, Wohlschlegel JA, Dreier L (Nov 2012). "Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy". The Journal of Biological Chemistry 287 (48): 40652–60. doi:10.1074/jbc.M112.419721. PMID 23060438.

Further reading

  • Verrier F, Mignotte B, Jan G, Brenner C (2004). "Study of PTPC composition during apoptosis for identification of viral protein target.". Ann. N. Y. Acad. Sci. 1010 (1): 126–42. doi:10.1196/annals.1299.022. PMID 15033708. 
  • McEnery MW, Snowman AM, Trifiletti RR, Snyder SH (1992). "Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier.". Proc. Natl. Acad. Sci. U.S.A. 89 (8): 3170–4. doi:10.1073/pnas.89.8.3170. PMC: 48827. PMID 1373486. 
  • Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
  • Jürgens L, Ilsemann P, Kratzin HD, Hesse D, Eckart K, Thinnes FP, Hilschmann N (1991). "Studies on human porin. IV. The primary structures of "Porin 31HM" purified from human skeletal muscle membranes and of "Porin 31HL" derived from human B lymphocyte membranes are identical.". Biol. Chem. Hoppe-Seyler 372 (7): 455–63. doi:10.1515/bchm3.1991.372.2.455. PMID 1657034. 
  • Kayser H, Kratzin HD, Thinnes FP, Götz H, Schmidt WE, Eckart K, Hilschmann N (1990). "[Identification of human porins. II. Characterization and primary structure of a 31-lDa porin from human B lymphocytes (Porin 31HL).]". Biol. Chem. Hoppe-Seyler 370 (12): 1265–78. PMID 2559745. 
  • Brdiczka D, Kaldis P, Wallimann T (1994). "In vitro complex formation between the octamer of mitochondrial creatine kinase and porin.". J. Biol. Chem. 269 (44): 27640–4. PMID 7525559. 
  • Yu WH, Wolfgang W, Forte M (1995). "Subcellular localization of human voltage-dependent anion channel isoforms.". J. Biol. Chem. 270 (23): 13998–4006. doi:10.1074/jbc.270.23.13998. PMID 7539795. 
  • Thomas L, Blachly-Dyson E, Colombini M, Forte M (1993). "Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel.". Proc. Natl. Acad. Sci. U.S.A. 90 (12): 5446–9. doi:10.1073/pnas.90.12.5446. PMC: 46737. PMID 7685903. 
  • Blachly-Dyson E, Zambronicz EB, Yu WH, Adams V, McCabe ER, Adelman J, Colombini M, Forte M (1993). "Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel.". J. Biol. Chem. 268 (3): 1835–41. PMID 8420959. 
  • Schleiff E, Shore GC, Goping IS (1997). "Human mitochondrial import receptor, Tom20p. Use of glutathione to reveal specific interactions between Tom20-glutathione S-transferase and mitochondrial precursor proteins.". FEBS Lett. 404 (2-3): 314–8. doi:10.1016/S0014-5793(97)00145-2. PMID 9119086. 
  • Reymann S, Haase W, Krick W, Burckhardt G, Thinnes FP (1998). "Endosomes: another extra-mitochondrial location of type-1 porin/voltage-dependent anion-selective channels.". Pflugers Arch. 436 (3): 478–80. doi:10.1007/s004240050659. PMID 9644232. 
  • Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (1999). "Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria.". Proc. Natl. Acad. Sci. U.S.A. 95 (25): 14681–6. doi:10.1073/pnas.95.25.14681. PMC: 24509. PMID 9843949. 
  • Crompton M, Virji S, Ward JM (1999). "Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore.". Eur. J. Biochem. 258 (2): 729–35. doi:10.1046/j.1432-1327.1998.2580729.x. PMID 9874241. 
  • Messina A, Oliva M, Rosato C, Huizing M, Ruitenbeek W, van den Heuvel LP, Forte M, Rocchi M, De Pinto V (1999). "Mapping of the human Voltage-Dependent Anion Channel isoforms 1 and 2 reconsidered.". Biochem. Biophys. Res. Commun. 255 (3): 707–10. doi:10.1006/bbrc.1998.0136. PMID 10049775. 
  • Shimizu S, Narita M, Tsujimoto Y (1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC.". Nature 399 (6735): 483–7. doi:10.1038/20959. PMID 10365962. 
  • Decker WK, Bowles KR, Schatte EC, Towbin JA, Craigen WJ (2000). "Revised fine mapping of the human voltage-dependent anion channel loci by radiation hybrid analysis.". Mamm. Genome 10 (10): 1041–2. doi:10.1007/s003359901158. PMID 10501981. 
  • Jacotot E, Ravagnan L, Loeffler M, Ferri KF, Vieira HL, Zamzami N, Costantini P, Druillennec S, Hoebeke J, Briand JP, Irinopoulou T, Daugas E, Susin SA, Cointe D, Xie ZH, Reed JC, Roques BP, Kroemer G (2000). "The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore.". J. Exp. Med. 191 (1): 33–46. doi:10.1084/jem.191.1.33. PMC: 2195797. PMID 10620603. 
  • Shimizu S, Tsujimoto Y (2000). "Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity.". Proc. Natl. Acad. Sci. U.S.A. 97 (2): 577–82. doi:10.1073/pnas.97.2.577. PMC: 15372. PMID 10639121. 
  • Stadtmüller U, Eben-Brunnen J, Schmid A, Hesse D, Klebert S, Kratzin HD, Hesse J, Zimmermann B, Reymann S, Thinnes FP, Benz R, Götz H, Hilschmann N (2000). "Mitochondria-derived and extra-mitochondrial human type-1 porin are identical as revealed by amino acid sequencing and electrophysiological characterisation.". Biol. Chem. 380 (12): 1461–6. doi:10.1515/BC.1999.189. PMID 10661876. 

External links

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