The voltage-dependent anion channel (VDAC): function in intracellular signalling, cell life and cell death

Curr Pharm Des. 2006;12(18):2249-70. doi: 10.2174/138161206777585111.


Research over the last decade has extended the prevailing view of mitochondria to include functions well beyond the critical bioenergetics role in supplying ATP. It is now recognized that mitochondria play a crucial role in cell signaling events, inter-organelle communication, aging, many diseases, cell proliferation and cell death. Apoptotic signal transmission to the mitochondria results in the efflux of a number of potential apoptotic regulators to the cytosol that trigger caspase activation and lead to cell destruction. Accumulating evidence indicates that the voltage-dependent anion channel (VDAC) is involved in this release of proteins via the outer mitochondrial membrane. VDAC in the outer mitochondrial membrane is in a crucial position in the cell, forming the main interface between the mitochondrial and the cellular metabolisms. VDAC has been recognized as a key protein in mitochondria-mediated apoptosis since it is the proposed target for the pro- and anti-apoptotic Bcl2-family of proteins and due to its function in the release of apoptotic proteins located in the inter-membranal space. The diameter of the VDAC pore is only about 2.6-3 nm, which is insufficient for passage of a folded protein like cytochrome c. New work suggests pore formation by homo-oligomers of VDAC or hetero-oligomers composed of VDAC and pro-apoptotic proteins such as Bax or Bak. This review provides insights into the central role of VDAC in cell life and death and emphasizes its function in the regulation of mitochondria-mediated apoptosis and, thereby, its potential as a rational target for new therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis* / drug effects
  • Arsenic Trioxide
  • Arsenicals / pharmacology
  • Arsenicals / therapeutic use
  • Calcium / metabolism
  • Cytochromes c / metabolism
  • Humans
  • Ion Channel Gating / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oxides / pharmacology
  • Oxides / therapeutic use
  • Permeability
  • Protein Conformation
  • Protein Folding
  • Protein Isoforms / chemistry
  • Protein Isoforms / drug effects
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Ruthenium Red / pharmacology
  • Signal Transduction* / drug effects
  • Voltage-Dependent Anion Channels / chemistry
  • Voltage-Dependent Anion Channels / drug effects
  • Voltage-Dependent Anion Channels / metabolism*
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents
  • Arsenicals
  • Oxides
  • Protein Isoforms
  • Proto-Oncogene Proteins c-bcl-2
  • Voltage-Dependent Anion Channels
  • bcl-2-Associated X Protein
  • Ruthenium Red
  • Cytochromes c
  • Arsenic Trioxide
  • Calcium