Hexokinase 2–Voltage-Dependent Anion Channel protein–protein interface (HK2–VDAC PPI)

The Hexokinase 2–Voltage-Dependent Anion Channel (HK2–VDAC) protein–protein interface is a pivotal metabolic and survival hub in many cancer cells, facilitating the Warburg effect (Pedersen, 2008). Hexokinase 2 (HK2) binds to VDAC1 on the outer mitochondrial membrane, allowing it to preferentially utilize mitochondrially generated ATP to phosphorylate glucose, thereby driving high glycolytic flux (Shoshan-Barmatz et al., 2015). This interaction also serves a potent anti-apoptotic function by preventing the release of cytochrome c and other pro-apoptotic factors from the mitochondria (Galluzzi et al., 2008). Because HK2 is highly overexpressed in many aggressive cancers but has limited expression in most healthy adult tissues, this interface represents a selective therapeutic target (Wolf et al., 2011). Pharmacological disruption of the HK2–VDAC complex causes HK2 to dissociate from the mitochondria, leading to metabolic reprogramming and the induction of apoptosis in malignant cells.

Other names

HK2-VDAC complexHexokinase II-VDAC interactionHKII-VDAC1 interfaceMitochondrial-bound hexokinase 2

Disruption of the protein-protein interaction between Hexokinase 2 and the Voltage-Dependent Anion Channel, leading to the dissociation of Hexokinase 2 from the outer mitochondrial membrane, which promotes apoptosis and inhibits the Warburg effect.