Journal of Bioenergetics and Biomembranes

, Volume 40, Issue 3, pp 123–126 | Cite as

Voltage dependent anion channels (VDACs): a brief introduction with a focus on the outer mitochondrial compartment’s roles together with hexokinase-2 in the “Warburg effect” in cancer

  • Peter L. PedersenEmail author


In recent years there has been renewed interest and focus on mitochondria of animal and human tissues. This interest commenced in the latter part of the past century and has gained momentum during the first eight years of this new millennium. The well accepted reason is that mitochondria are now recognized to represent not only “power houses“, i.e., the ATP production factories of tissues essential for cell life, but in response to a variety of different “cues” may participate significantly also in cell death, both that associated with normal turnover and that associated with disease. Conversely, in cancers (particularly the advanced) their mitochondria interact with hexokinase 2 (HK-2) resulting in suppression of cell death while supporting cell growth via enhanced glycolysis, even in the presence of oxygen (Warburg effect). The identification/elucidation of proteins and mechanisms involved in deciding and/or participating in cell fate (i.e., life, death, or cancer) has focused to a large extent on the mitochondrial outer compartment, which is taken here to collectively include the outer membrane, the space between the inner and outer membranes, and contact regions between these two membranes. Among the established proteins believed to be involved in events related to cell fate are “VDACs” that form the basis of this mini-review series. This brief introductory review focuses mainly on the past discovery by the author and colleagues that VDAC located within the outer mitochondrial compartment and its binding partner HK-2 are pivotal players in the “Warburg effect” in cancer. As one case in point, when glucose is added to liver cytosol (mitochondria-free) the rate of glycolysis is very low. However, upon addition of tumor mitochondria containing VDAC bound HK-2, the low glycolytic rate is increased to a high rate near that catalyzed by the tumor cytoplasm from which the tumor mitochondria were derived.


VDAC Hexokinase-2 Mitochondria Cancer Warburg effect Glycolysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Al Jamal JA (2005) Protein J 24:1–8CrossRefGoogle Scholar
  2. Arora KK, Pedersen PL (1988) J Biol Chem 263:17422–17428Google Scholar
  3. Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007) Nat Cell Biol 9:550–555CrossRefGoogle Scholar
  4. Bustamante E, Pedersen PL (1977) Proc Nat Acad Sci USA 74:3735–3739CrossRefGoogle Scholar
  5. Bustamante E, Pedersen PL (1980) Biochemistry 19:4972–4977CrossRefGoogle Scholar
  6. Bustamante E, Morris HP, Pedersen PL (1978) Adv Exp Biol Med 92:363–380Google Scholar
  7. Bustamante E, Morris HP, Pedersen PL (1981) J Biol Chem 256:8699–8704Google Scholar
  8. Chen C, Ko Y, Delannoy M, Ludtke SJ, Chiu W, Pedersen PL (2004) J Biol Chem 279:31761–31768CrossRefGoogle Scholar
  9. Chiara F, Castellaro D, Marin O, Petronilli V, Brusilow WS, Juhaszova M, Sollott SJ, Forte M, Bernardi P, Rasola A (2008) PLOS ONE 3:e1852CrossRefGoogle Scholar
  10. Colombini M (2007) Methods Cell Biol 12:835–840Google Scholar
  11. DiChiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP (1982) Neurology 32:1323–1329Google Scholar
  12. Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N (2001) Genes Dev 15:1406–1418CrossRefGoogle Scholar
  13. Han D, Antures F, Canali R, Rettori D, Cadenas E (2003) J Biol Chem 278:5557–5563CrossRefGoogle Scholar
  14. Indo T, Wan CN, Casella V et al (1978) J Label Compds Radiopharm 24:174–183Google Scholar
  15. Jiang X, Wang X (2004) Annu Rev Biochem 73:87–106CrossRefGoogle Scholar
  16. Jiang JY, Han CR, Jeong YJ, Kim HJ, Lim HS, Lee KH, Park HO, Oh WM, Kim SH Kim WJ (2007a) Neurosci Lett 411:222–227CrossRefGoogle Scholar
  17. Jing W, Du B, Chi Z, Ma L, Wang S, Zhang X, Wu W, Wang X, Xu G, Guo C (2007b) J Neurosci Res 85:3160–3170CrossRefGoogle Scholar
  18. Kikuchi T, Yoshida Y, Morioka T, Gejyo F, Oite T (2008) Mod Rheumatol June 21 (in press)Google Scholar
  19. Ko YH, Delannoy M, Hullihen J, Chiu W, Pedersen PL (2003) J Biol Chem 278:12305–12309CrossRefGoogle Scholar
  20. Lemaster JJ, Holmuhamedov E (2006) Biochim Biophys Acta 1762:181–190Google Scholar
  21. Marin R, Ramirez CM, Gonzalez M, Gonzalez-Munoz E, Zorzano A, Camps M, Alonzo R, Diaz M (2007) Mol Membr Biol 24:148–1460CrossRefGoogle Scholar
  22. Mathupala SP, Ko YH, Pedersen PL (2006) Oncogene 25:4777–4786CrossRefGoogle Scholar
  23. Nakashima RA, Mangan PS, Colombini M, Pedersen PL (1986) Biochemistry 25:1015–10121CrossRefGoogle Scholar
  24. Nakashima RA, Paggi MG, Scott LJ, Pedersen PL (1988) Can Res 48:913–919Google Scholar
  25. Neuzil J, Wang X-F, Dong L-F, Low P, Ralph SJ (2006) FEBS Lett 580:5125–5129CrossRefGoogle Scholar
  26. Pastorino JG, Shulga N, Hoek JB (2002) J Biol Chem 277:7610–7618CrossRefGoogle Scholar
  27. Rose IA, Warms JV (1967) J Biol Chem 242:1635–1645Google Scholar
  28. Sampson MJ, Lowell RS, Craigen WJ (1997) J Biol Chem 272:18966–18973CrossRefGoogle Scholar
  29. Shoshan-Barmatz V, Israelson A, Brdiczka D, Shew SS (2006) Curr Pharm Des 12:2249–2270CrossRefGoogle Scholar
  30. Warburg O (1930) The metabolism of tumours. London. ConstableGoogle Scholar
  31. Warburg O (1956) Science 124:269–270Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Biological ChemistryJohns Hopkins University, School of MedicineBaltimoreUSA

Personalised recommendations