Voltage-dependent anion-selective channel protein 2–Apoptosis regulator BAX protein–protein interface (VDAC2–BAX interface)

The VDAC2–BAX protein–protein interface is a critical regulatory site for the intrinsic apoptotic pathway, located on the mitochondrial outer membrane (PubMed: 25242322). Voltage-dependent anion-selective channel protein 2 (VDAC2) acts as a mitochondrial anchor for the pro-apoptotic protein BAX (Bcl-2-associated X protein), facilitating its recruitment and subsequent activation (UniProt: P45880). Under normal physiological conditions, VDAC2 is essential for BAX-mediated apoptosis, as its absence significantly impairs BAX translocation and pore formation (PubMed: 31434674). Upon apoptotic signaling, the interaction facilitates BAX oligomerization and mitochondrial outer membrane permeabilization (MOMP), leading to the release of cytochrome c and other pro-apoptotic factors into the cytosol (PubMed: 25242322). In many cancers, the VDAC2–BAX interaction is a focal point for evading apoptosis, making it an attractive target for small-molecule sensitizers. Research has identified small molecules like WEHI-9625 that specifically bind VDAC2 to enhance BAX-mediated killing in certain cancer types, such as melanoma (Nature Chemical Biology: van Delft et al., 2014). Conversely, in neurodegenerative diseases or ischemic injury, inhibiting this interface could potentially preserve cell viability by preventing BAX-induced mitochondrial damage (PubMed: 31434674).

Other names

VDAC2-BAX complexVDAC2-BAX interactionVDAC2-BAX protein-protein interaction

Small molecule modulation of the VDAC2-BAX interaction to either facilitate or inhibit BAX recruitment, oligomerization, and subsequent mitochondrial outer membrane permeabilization (MOMP).