Voltage dependent anion channel-1 (VDAC-1) as an anti-cancer target.

Voltage dependent anion channels (VDACs) are pore-forming proteins (approximately 30 kDa) associated with mitochondria, the membrane-bound organelles found in almost all eukaryotes. Commonly referred to as the “power-generators of cells”, mitochondria are composed of binary membranes, an outer membrane (OMM; outer mitochondrial membrane) and an inner membrane (IMM; inner mitochondrial membrane). While the latter is essentially impermeable to hydrophilic solutes of any kind, the OMM is made “porous” by the VDACs, which are integral membrane proteins that facilitate the free diffusion of molecules of approximately 5 kDa or less. Thus, the presence of VDACs (aptly named the “porins”),1 were used to explain the high solute permeability of the OMM, and its unresponsiveness to osmotic pressures. Electron micrographs of the OMM also display a porous appearance (reviewed by Mannella and Kinnaly, 2008)2 with a near-crystalline array of pores visible in lipid depleted OMMs. It should be noted that larger proteins encoded by nuclear DNA (and destined for the mitochondrion via an N-terminal signal sequence), bind to specialized “translocating protein complexes” on the OMM and are then transported across. The OMM also associates with the endoplasmic reticulum (ER) to facilitate transport of specific solutes, including lipids.