Hexokinase–VDAC complex

The hexokinase–VDAC complex refers to the physical and functional association between hexokinase isoforms (especially hexokinase-I and hexokinase-II) and the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. This interaction facilitates direct access of hexokinase to mitochondrial ATP, thereby supporting efficient glycolysis. Binding of hexokinase also confers protection against apoptosis by preventing the association of pro-apoptotic proteins (such as Bax) with the mitochondria and by modulating the mitochondrial permeability transition pore. The complex is particularly abundant in cancer cells due to upregulated hexokinase-II, promoting the metabolic phenotype known as the Warburg effect. Disruption of this protein–protein interaction sensitizes cells to cell death, making the hexokinase–VDAC complex an attractive, though challenging, therapeutic target for cancer and possibly other diseases involving mitochondrial dysfunction.

Other names

Mitochondrially-bound hexokinase–VDAC complexHexokinase–voltage-dependent anion channel complexHK–VDAC complexMitochondrial hexokinase–VDAC complex

Inhibitors disrupt binding of hexokinase to VDAC, promoting apoptosis and sensitizing cells (notably cancer cells) to cell death