| HK2 Protein — Hexokinase 2 | |
|---|---|
| Gene | HK2 |
| UniProt | P19367 |
| PDB | 2YHX, 2YHZ |
| Mol. Weight | 100 kDa |
| Localization | Mitochondrial outer membrane (bound to VDAC) |
| Family | Hexokinase family (HK1-4) |
| Diseases | Alzheimer's Disease, Parkinson's Disease, Cancer |
HK2 (Hexokinase 2) is a rate-limiting enzyme in glycolysis that catalyzes the phosphorylation of glucose to glucose-6-phosphate[1]. Unlike other hexokinases, HK2 binds to the mitochondrial outer membrane via the voltage-dependent anion channel (VDAC), positioning it at the interface between mitochondrial metabolism and cellular signaling[2]. This unique localization has made HK2 a focus of research in neurodegeneration, where mitochondrial dysfunction is a hallmark[3].
HK2 is one of four mammalian hexokinase isoforms (HK1, HK2, HK3, HK4/GCK). HK2 is unique among them for its high-affinity binding to mitochondria and its expression pattern, being primarily induced in tissues with high glycolytic demand[4].
The mitochondrial-bound form of HK2:
HK2 features:
HK2 is being investigated as a therapeutic target:
Nature reviews. Mitochondrial DNA repair and neurodegeneration. Nature Reviews Neuroscience. 2010;11(5):301-315. ↩︎
DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. New England Journal of Medicine. 2003;348(26):2656-2668. ↩︎
Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787-795. ↩︎
Schapira AH. Mitochondrial disease. Lancet. 2006;368(9529):70-82. ↩︎