Voltage-dependent anion channel protein (VDAC)

The voltage-dependent anion channel protein (VDAC) is the primary pore-forming protein of the outer mitochondrial membrane, essential for the metabolite and ion exchange between the mitochondria and cytosol in eukaryotic cells. It is a β-barrel membrane protein comprised of about 280 amino acids, with three main isoforms in mammals (VDAC1–3). VDAC is integral to cellular metabolism by facilitating the passage of ATP, ADP, NADH, and inorganic ions, and it is central to the control of apoptosis via interactions with pro- and anti-apoptotic proteins (e.g., Bcl-2 family, hexokinase). VDAC is implicated in numerous diseases, especially through its roles in mitochondrial dysfunction, metabolic reprogramming, and apoptotic signaling. The structure enables voltage-dependent gating, switching between open (anion-selective) and closed (slightly cation-selective) states, regulated by voltage and protein–ligand interactions. VDAC’s function as a metabolic gatekeeper and apoptotic modulator makes it an important pharmacological and therapeutic target in cancer and neurodegenerative disease research, with several small-molecule modulators under investigation or use.

Other names

Voltage-dependent anion channelVDACMitochondrial porinPorin, mitochondrialVoltage-dependent anion-selective channel

Apoptosis induction by modulating channel permeability (permeabilization allows release of apoptogenic factors); Inhibition of metabolic exchange (e.g., blocking ATP/ADP flow); Alteration of mitochondrial membrane potential; Chemical inhibition or stabilization of channel open/closed states as means of cytotoxic or cytoprotective action