Voltage-dependent anion-selective channel 1 (VDAC1)

Voltage-dependent anion-selective channel 1 (VDAC1) is a 19-strand beta-barrel protein that serves as the primary "gatekeeper" of the outer mitochondrial membrane (OMM) [9, 12, 15]. It functions as a critical conduit for the exchange of ions and metabolites—most notably ATP and ADP—between the mitochondria and the cytoplasm, thereby regulating cellular energy homeostasis and bioenergetics [2, 9, 20]. Beyond its role in metabolism, VDAC1 is central to the intrinsic pathway of apoptosis; under stress or specific signaling, VDAC1 can undergo oligomerization to form large pores that facilitate the release of pro-apoptotic factors like cytochrome c into the cytosol [1, 5, 7]. In many cancers, VDAC1 is significantly overexpressed, where it associates with proteins such as hexokinase and Bcl-2 to promote a high glycolytic rate and provide resistance to cell death [12, 13, 20]. Conversely, in neurodegenerative diseases like Alzheimer's and Parkinson's, pathological VDAC1 oligomerization and calcium dysregulation contribute to premature neuronal loss [15, 18]. Therapeutic strategies involving VDAC1 include small molecules like erastin that induce ferroptotic cell death in tumors, and inhibitors like VBIT-4 that prevent oligomerization to protect cells from neurodegeneration and inflammation [7, 18, 19].

Other names

VDAC-1Porin 1Mitochondrial porin31HL31HMPlasmalemmal porinOuter mitochondrial membrane protein porin 1Sperm binding protein 1a

Modulation of VDAC1 channel gating, oligomerization, or protein-protein interactions (e.g., with HK-II or Bcl-2) to regulate mitochondrial metabolite exchange and the release of pro-apoptotic factors.