Article

Journal of Bioenergetics and Biomembranes

, Volume 40, Issue 3, pp 183-191

Uncovering the role of VDAC in the regulation of cell life and death

  • Varda Shoshan-BarmatzAffiliated withDepartment of Life Sciences, Ben-Gurion University of the NegevThe National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev Email author 
  • , Nurit KeinanAffiliated withDepartment of Life Sciences, Ben-Gurion University of the NegevThe National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev
  • , Hilal ZaidAffiliated withDepartment of Life Sciences, Ben-Gurion University of the NegevThe National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.

Keywords

Apoptosis Cancer Cytochrome c Hexokinase Mitochondria shRNA VDAC