Voltage-dependent anion-selective channel protein (VDAC)

Voltage-dependent anion-selective channel protein (VDAC) is the most abundant protein in the outer mitochondrial membrane and forms a hydrophilic, voltage-gated pore that enables the exchange of metabolites and ions between the mitochondria and the cytosol[1][2][4]. VDAC exists in three major isoforms in mammals (VDAC1, VDAC2, VDAC3), each with distinct regulatory properties but a conserved β-barrel structure composed of 19 strands[3][4]. The channel is critical for mitochondrial metabolism, apoptosis regulation (by controlling cytochrome c release), and calcium signaling, and it interacts with a wide range of proteins (including hexokinase, Bcl-2 family members, and others)[1][2]. VDACs are considered attractive therapeutic targets for modulating mitochondrial-induced cell death, with implications for cancer therapy and neurodegenerative disorders, but their fundamental role in cellular metabolism presents significant therapeutic challenges and safety considerations[2][4].

Other names

Voltage-dependent anion channelMitochondrial porinVDAC1 (for isoform 1)VDAC2 (for isoform 2)VDAC3 (for isoform 3)

Channel blockade to inhibit metabolite and Ca^2+^ flux. Induction of apoptosis via disruption of mitochondrial membrane potential and cytochrome c release. Inhibition/activation of ATP/ADP exchange, affecting cellular energetics. Modulation of ferroptosis by altering redox status or interacting proteins.