VDAC2
Description
The VDAC2 (voltage dependent anion channel 2) is a protein-coding gene located on chromosome 10.
Voltage-dependent anion-selective channel protein 2 (VDAC2) is a protein encoded by the VDAC2 gene on chromosome 10 in humans. It shares structural similarities with other VDAC isoforms and plays a critical role in regulating cell metabolism, mitochondrial apoptosis, and spermatogenesis. VDAC2 also participates in cardiac contractions and pulmonary circulation, linking it to cardiopulmonary diseases. Additionally, it mediates immune response to infectious bursal disease (IBD). The three human VDAC isoforms exhibit high conservation, especially in their 3D structure. VDACs form a wide β-barrel structure, with the N-terminal residing inside to partially close the pore. The VDAC2 isoform contains a high abundance of cysteines, contributing to the formation of disulfide bridges and influencing the flexibility of the β-barrel. VDACs also possess a mitochondrial targeting sequence for translocation to the outer mitochondrial membrane. Notably, VDAC2's N-terminal is 11 residues longer compared to the other two isoforms.
VDAC2 forms a channel through the outer mitochondrial membrane, facilitating the passage of small hydrophilic molecules. This channel dynamically shifts between open and closed conformations based on membrane potential. At low or zero potential, the channel is open and exhibits weak anion selectivity. However, at potentials exceeding 30-40 mV, the channel closes and becomes cation-selective. VDAC2 interacts with various lipids, including ceramide, phosphatidylcholine, cholesterol, and oxysterol. The binding of ceramide to VDAC2 is particularly noteworthy, as it triggers the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway.
VDAC2 is also known as POR.
