Voltage-dependent anion-selective channel 2 (VDAC2) and Voltage-dependent anion-selective channel 3 (VDAC3) (VDAC2, VDAC3)

Voltage-dependent anion-selective channel 2 and 3 are mitochondrial outer membrane proteins belonging to the porin family. **VDAC2** shares many functions with other VDAC isoforms but is distinguished by its prominent role in facilitating mitochondrial calcium uptake, modulating apoptosis through regulation of Bak, and unique structural motifs (notably a longer N-terminal sequence and additional cysteine residues) that may be important for isoform-specific roles[5][6]. **VDAC3**, though highly homologous in structure to VDAC1 and VDAC2, demonstrates less abundant expression, unique electrophysiological properties (smaller, less voltage-gated conductance), and a prominent role in sperm flagellum organization and centrosome function, as well as sensing the oxidative state in mitochondria via redox-sensitive cysteine residues[4][1][8][2]. Both VDAC2 and VDAC3 serve as metabolic and apoptotic gatekeepers at the mitochondrial outer membrane by controlling ionic and metabolic flux, interacting with essential cell death proteins, and contributing to cellular energetic homeostasis and stress responses[3][5][4].

Other names

VDAC2: Voltage-dependent anion channel 2VDAC3: Voltage-dependent anion channel 3Outer mitochondrial membrane pore protein (OMMPP2/3)Porin 2/3

Induction of mitochondrial outer membrane permeabilization (MOMP) via interaction with pro-apoptotic Bcl-2 family proteins (e.g., Bak–VDAC2 interaction regulates Bak activation and apoptosis)[6]. Blockage of VDAC pore by interacting proteins (e.g., hexokinase, tubulin) to regulate metabolite flow and cell survival[3][9]. Modulation of channel gating by redox modifications or binding partners (VDAC3)[8].