Hexokinase 2–voltage-dependent anion channel 1 complex (HK2–VDAC1 complex)

The **hexokinase 2–voltage-dependent anion channel 1 complex (HK2–VDAC1 complex)** is a molecular assembly formed by the binding of hexokinase 2 (HK2), a key glycolytic enzyme, to voltage-dependent anion channel 1 (VDAC1), a pore-forming protein on the outer mitochondrial membrane[1][3][6]. This complex localizes primarily at mitochondria-associated membranes (MAMs), sites of close contact between mitochondria and the endoplasmic reticulum[2][5]. Binding of HK2 to VDAC1 facilitates direct access to intramitochondrial ATP, enabling high rates of glycolysis and supporting cancer cell metabolism[6]. The HK2–VDAC1 interaction also protects cells—especially tumor cells—from apoptosis by preventing the release of apoptogenic factors from mitochondria[3][6]. Disruption of this complex (e.g., by specific inhibitors or displacing peptides) can sensitize cancer cells to cell death and is an emerging therapeutic strategy for cancers and potentially other diseases involving dysregulated metabolism and mitochondrial function[5][6]. The HK2–VDAC1 interaction is also implicated in the regulation of intracellular calcium flux and mitochondrial permeability transition, relevant for inflammation and cell death signaling[2].

Other names

Hexokinase-II–VDAC complexHK2–VDAC complexHexokinase 2–VDAC complexHexokinase 2–VDAC1 complex

Disruption of HK2–VDAC1 binding induces apoptosis in cancer cells by permitting pro-apoptotic factor release from mitochondria and reducing glycolytic flux[3][6]. Inhibition of HK2 enzymatic activity deprives cancer cells of ATP required for rapid growth and survival[6]. Peptides targeting the HK2–VDAC interface dislodge HK2 from mitochondria, increase mitochondrial membrane permeability, and trigger cell death in tumors[5].