The VDAC2 protein belongs to a group of mitochondrial membrane channels involved in translocation of
adenine nucleotides through the outer membrane. These channels may also function as a mitochondrial binding site for
hexokinase and
glycerol kinase. The VDAC is an important constituent in apoptotic signaling and
oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling. Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis.
Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics a normal
embryologic processes, or during cell injury (such as ischemia-reperfusion injury during
heart attacks and
strokes) or during developments and processes in
cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the
DNA and
nucleus. This is followed by fragmentation into
apoptotic bodies that are quickly removed by
phagocytes, thereby preventing an
inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite
mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain
nuclear and or
cytoplasmic elements. The ultrastructural appearance of
necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many
physiological and
pathological processes. It plays an important role during
embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. The VDAC2 protein has been implicated in cardioprotection against ischemia-reperfusion injury, such as during
ischemic preconditioning of the heart. Although a large burst of
reactive oxygen species (ROS) is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage. It has even been observed that during this release of reactive oxygen species, VDAC2 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and cell death. The VDAC2 protein has been linked persistent pulmonary hypertension of the newborn (PPHN), which causes a large majority of neonatal morbidity and mortality, due to its role as a major regulator of endothelium-dependent nitric oxide synthase (eNOS) in the pulmonary endothelium. eNOS has been attributed with regulating NOS activity in response to physiological stimuli, which is vital to maintain NO production for proper blood circulation to the lungs. As a result, VDAC2 is significantly involved in pulmonary circulation and may become a therapeutic target for treating diseases such as pulmonary hypertension, VDAC2 may also serve an immune function, as it has been hypothesized to detect and induce apoptosis in cells infected by the IBD virus. IBD, the equivalent HIV in birds, can compromise their immune systems and even cause fatal injury to the lymphoid organ, Studies of this process indicate that VDAC2 interacts with the viral protein V5 to mediate cell death. == Interactions ==