Non-selective voltage-gated ion channel VDAC1

VDAC1 (voltage-dependent anion channel 1) is a non-selective ion channel that mediates transport of anions and cations across the outer mitochondrial membrane and plasma membrane (UniProt: P21796). The channel adopts voltage-dependent conformations—open at low potential with weak anion selectivity, and closed at higher potentials with cation selectivity. It regulates diffusion of small hydrophilic molecules and participates in cell volume regulation and apoptosis signaling.

VDAC1 is embedded in critical mitochondrial processes including mitophagy downstream of PRKN/PINK1, permeability transition pore formation, and calcium-dependent apoptosis via interaction with HSPA9 and ITPR1 (UniProt: P21796). The protein also mediates cytochrome c efflux and catalyzes phospholipid scrambling across the outer mitochondrial membrane. It binds regulatory lipids including ceramide, phosphatidylcholine, and cholesterol.

In Alzheimer's disease, VDAC1 shows ambiguous regulation across subcellular fractions of post-mortem AD brain tissue (mean log2FC = 0.46, 2 of 4 fractions measured; Chaparral AD proteomics). This modest and directionally inconsistent signal across fractions suggests context-dependent or compartment-specific changes in AD pathology, warranting further investigation of VDAC1's role in mitochondrial dysfunction and neurodegeneration.