The voltage gated anion selective channel (VDAC) is the major protein in the mitochondrial outer membrane. This protein provides the pathway by which metabolites are exchanged between the mitochondria and the cytosol. The VDAC channel can exist in a highly conductive open state at low membrane potentials or in a low conductive closed state at high membrane potentials. It has been found that a soluble protein or group of proteins from the mitochondrial intermembrane space can regulate the opening and closing of the VDAC channel. The importance of VDAC in the well being of humans has been shown. The few children with reduced VDAC expression were severely deformed and died at an early age. Mice missing the VDAC1 gene suffer from myopathy. Mice missing the VDAC3 gene have non-motile sperm. There are also indicators that VDAC may be involved in apoptosis. By identifying what protein or group of proteins act as the VDAC modulator, we an determine how VDAC is regulated. At the very least, we can identify the cast of characters. After identification of the modulator components, the effect of presence and absence of each will be observed in vitro and in vivo. Thus the role of VDAC modulator proteins in mitochondrial functioning will begin to be elucidated.
