Abstract
Proper cell activity requires an efficient exchange of molecules between mitochondria and cytoplasm. Lying in the outer mitochondrial membrane, VDAC assumes a crucial position in the cell, forming the main interface between the mitochondrial and the cellular metabolisms. As such, it has been recognized that VDAC plays a crucial role in regulating the metabolic and energetic functions of mitochondria. Indeed, down-regulation of VDAC1 expression by shRNA leads to a decrease in energy production and cell growth. VDAC has also been recognized as a key protein in mitochondria-mediated apoptosis through its involvement in the release of apoptotic proteins located in the inter-membranal space and as the proposed target of pro- and anti-apoptotic members of the Bcl2-family and of hexokinase. Questions, however, remain as to if and how VDAC mediates the transfer of apoptotic proteins from the inter-membranal space to the cytosol. The diameter of the VDAC pore is only about 2.5–3 nm, insufficient for the passage of a folded protein like cytochrome c. New work, however, suggests that pore formation involves the assembly of homo-oligomers of VDAC or hetero-oligomers composed of VDAC and pro-apoptotic proteins, such as Bax. Thus, VDAC appears to represent a convergence point for a variety of cell survival and cell death signals. This review provides insight into the central role of VDAC in mammalian cell life and death, emphasizing VDAC function in the regulation of mitochondria-mediated apoptosis and, as such, its potential as a rational target for new therapeutics.
Similar content being viewed by others
References
Abu-Hamad S, Sivan S, Shoshan-Barmatz V (2006) Proc Natl Acad Sci U S A 103:5787–5792
Abu-Hamad S, Zaid H, Israelson A, Nahon E, Shoshan-Barmatz V (2008) J Biol Chem 283(19):13482–13490
Azoulay-Zohar H, Israelson A, Abu-Hamad S, Shoshan-Barmatz V (2004) Biochem J 377:347–355
Bae JH, Park JW, Kwon TK (2003) Biochem Biophys Res Commun 303:1073–1079
Baek JH, Lee YS, Kang CM, Kim JA, Kwon KS, Son HC, Kim KW (1997) Int J Cancer 73:725–728
Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007) Nat Cell Biol 9:550–555
Banerjee J, Ghosh S (2004) Biochem Biophys Res Commun 323:310–314
Bathori G, Sahin-Toth M, Fonyo A, Ligeti E (1993) Biochim Biophys Acta 1145:168–176
Bathori G, Csordas G, Garcia-Perez C, Davies E, Hajnoczky G (2006) J Biol Chem 281:17347–17358
Bryson JM, Coy PE, Gottlob K, Hay N, Robey RB (2002) J Biol Chem 277:11392–11400
Colombini M (2004) Mol Cell Biochem 256–257:107–115
De Pinto V, Messina A, Accardi R, Aiello R, Guarino F, Tomasello MF, Tommasino M, Tasco G, Casadio R, Benz R, De Giorgi F, Ichas F, Baker M, Lawen A (2003) Ital J Biochem 52:17–24
Deniaud A, Rossi C, Berquand A, Homand J, Campagna S, Knoll W, Brenner C, Chopineau J (2007) Langmuir 23:3898–3905
Ding WX, Shen HM, Ong CN (2001) Biochem Biophys Res Commun 285:1155–1161
Doran E, Halestrap AP (2000) Biochem J 348:343–350
Fanciulli M, Paggi MG, Bruno T, Del Carlo C, Bonetto F, Gentile FP, Floridi A (1994) Oncol Res 6:405–409
Florke H, Thinnes FP, Winkelbach H, Stadtmuller U, Paetzold G, Morys-Wortmann C, Hesse D, Sternbach H, Zimmermann B, Kaufmann-Kolle P (1994) Biol Chem Hoppe-Seyler 375:513–520
Gelb BD, Adams V, Jones SN, Griffin LD, MacGregor GR, McCabe ER (1992) Proc Natl Acad Sci U S A 89:202–206
Geschwind JF, Ko YH, Torbenson MS, Magee C, Pedersen PL (2002) Cancer Res 62:3909–3913
Ghosh T, Pandey N, Maitra A, Brahmachari SK, Pillai B (2007) PLoS ONE 2:e1170
Gincel D, Shoshan-Barmatz V (2004) J Bioenerg Biomembr 36:179–186
Gincel D, Silberberg SD, Shoshan-Barmatz V (2000) J Bioenerg Biomembr 32:571–583
Gincel D, Zaid H, Shoshan-Barmatz V (2001) Biochem J 358:147–155
Godbole A, Varghese J, Sarin A, Mathew MK (2003) Biochim Biophys Acta 1642:87–96
Goldin N, Arzoine L, Heyfets A, Israelson A, Zaslavsky Z, Bravman T, Bronner V, Notcovich A, Shoshan-Barmatz V, Flescher E (2008) Oncogene (in press)
Goncalves RP, Buzhynskyy N, Prima V, Sturgis JN, Scheuring S (2007) J Mol Biol 369:413–418
Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N (2001) Genes Dev 15:1406–1418
Granville DJ, Gottlieb RA (2003) Curr Med Chem 10:1527–1533
Gunter TE, Buntinas L, Sparagna GC, Gunter KK (1998) Biochim Biophys Acta 1366:5–15
Halestrap AP, Doran E, Gillespie JP, O’Toole A (2000) Biochem Soc Trans 28:170–177
Halestrap AP, McStay GP, Clarke SJ (2002) Biochimie 84:153–166
Hoogenboom BW, Suda K, Engel A, Fotiadis D (2007) J Mol Biol 370:246–255
Israelson A, Arzoine L, Abu-hamad S, Khodorkovsky V, Shoshan-Barmatz V (2005) Chem Biol 12:1169–1178
Israelson A, Abu-Hamad S, Zaid H, Nahon E, Shoshan-Barmatz V (2007a) Cell Calcium 41:235–244
Israelson A, Zaid H, Abu-Hamad S, Nahon E, Shoshan-Barmatz V (2007b) Cell Calcium 43:196–204
Juhaszova M, Wang S, Zorov DB, Bradley Nuss H, Gleichmann M, Mattson MP, Sollott SJ (2008) Ann N Y Acad Sci 1123:197–212
Kroemer G, Galluzzi L, Brenner C (2007) Physiol Rev 87:99–163
Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y (2000) Oncogene 19:4807–4814
Lee AC, Xu X, Colombini M (1996) J Biol Chem 271:26724–26731
Lemasters JJ (2007) J Gastroenterol Hepatol 22(Suppl 1):S31–S37
Lemasters JJ, Holmuhamedov E (2006) Biochim Biophys Acta 1762:181–190
Lu AJ, Dong CW, Du CS, Zhang QY (2007) Fish Shellfish Immunol 23:601–613
Madesh M, Hajnoczky G (2001) J Cell Biol 155:1003–1015
Malia TJ, Wagner G (2007) Biochemistry 46:514–525
Martinou JC, Desagher S, Antonsson B (2000) Nat Cell Biol 2:E41–E43
Mathupala SP, Ko YH, Pedersen PL (2006) Oncogene 25:4777–4786
Nakashima RA (1986) Biochemistry 25:1015–1021
Nichols BJ, Denton RM (1995) Mol Cell Biochem 149–150:203–212
Pastorino JG, Hoek JB (2003) Curr Med Chem 10:1535–1551
Pastorino JG, Shulga N, Hoek JB (2002) J Biol Chem 277:7610–7618
Pastorino JG, Hoek JB, Shulga N (2005) Cancer Res 65:10545–10554
Pedersen PL (2007) J Bioenerg Biomembr 39:211–222
Pedersen PL, Mathupala S, Rempel A, Geschwind JF, Ko YH (2002) Biochim Biophys Acta 1555:14–20
Robey RB, Hay N (2006) Oncogene 25:4683–4696
Rostovtseva TK, Komarov A, Bezrukov SM, Colombini M (2002) Biophys J 82:193–205
Rostovtseva TK, Tan W, Colombini M (2005) J Bioenerg Biomembr 37:129–142
Shi Y, Jiang C, Chen Q, Tang H (2003) Biochem Biophys Res Commun 303:475–482
Shimizu S, Narita M, Tsujimoto Y (1999) Nature 399:483–487
Shimizu S, Shinohara Y, Tsujimoto Y (2000a) Oncogene 19:4309–4318
Shimizu S, Ide T, Yanagida T, Tsujimoto Y (2000b) J Biol Chem 275:12321–12325
Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y (2001) J Cell Biol 152:237–250
Shoshan-Barmatz V, Gincel D (2003) Cell Biochem Biophys 39:279–292
Shoshan-Barmatz V, Israelson A (2005) J Membr Biol 204:57–66
Shoshan-Barmatz V, Zalk R, Gincel D, Vardi N (2004) Biochim Biophys Acta 1657:105–114
Shoshan-Barmatz V, Israelson A, Brdiczka D, Sheu SS (2006) Curr Pharm Des 12:2249–2270
Shoshan-Barmatz S, Arbel N, Arzoine L (2008) Cell Sci 4:74–118
Simamura E, Hirai K, Shimada H, Koyama J, Niwa Y, Shimizu S (2006) Cancer Biol Ther 5:1523–1529
Sui D, Wilson JE (1997) Arch Biochem Biophys 345:111–125
Sun L, Shukair S, Naik TJ, Moazed F, Ardehali H (2007) Mol Cell Biol 28(3):1007–1017
Tajeddine N, Galluzzi L, Kepp O, Hangen E, Morselli E, Senovilla L, Araujo N, Pinna G, Larochette N, Zamzami N, Modjtahedi N, Harel-Bellan A, Kroemer G (2008) Oncogene (in press)
Tan W, Colombini M (2007) Biochim Biophys Acta 1768(10):2510–2515
Tarze A, Deniaud A, Le Bras M, Maillier E, Molle D, Larochette N, Zamzami N, Jan G, Kroemer G, Brenner C (2007) Oncogene 26:2606–2620
Tsujimoto Y (2003) J Cell Physiol 195:158–167
Tsujimoto Y, Shimizu S (2002) Biochimie 84:187–193
Tsujimoto Y, Shimizu S (2007) Apoptosis 12:835–840
Vyssokikh MY, Brdiczka D (2003) Acta Biochim Pol 50:389–404
Wilson JE (2003) J Exp Biol 206:2049–2057
Yehezkel G, Hadad N, Zaid H, Sivan S, Shoshan-Barmatz V (2006) J Biol Chem 281:5938–5946
Yehezkel G, Abu-Hamad S, Shoshan-Barmatz V (2007) J Cell Physiol 212:551–561
Yu J, Qian H, Li Y, Wang Y, Zhang X, Liang X, Fu M, Lin C (2007) Cancer Biol Ther 6:580–586
Yuan S, Fu Y, Wang X, Shi H, Huang Y, Song X, Li L, Song N, Luo Y (2008) FASEB J (in press)
Zaid H, Abu-Hamad S, Israelson A, Nathan I, Shoshan-Barmatz V (2005) Cell Death Differ 12:751–760
Zalk R, Israelson A, Garty ES, Azoulay-Zohar H, Shoshan-Barmatz V (2005) Biochem J 386:73–83
Zheng Y, Shi Y, Tian C, Jiang C, Jin H, Chen J, Almasan A, Tang H, Chen Q (2004) Oncogene 23:1239–1247
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shoshan-Barmatz, V., Keinan, N. & Zaid, H. Uncovering the role of VDAC in the regulation of cell life and death. J Bioenerg Biomembr 40, 183–191 (2008). https://doi.org/10.1007/s10863-008-9147-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10863-008-9147-9