Creatine kinase S-type, mitochondrial (CKMT2)

Creatine kinase S-type, mitochondrial (CKMT2), also known as sarcomeric mitochondrial creatine kinase, is an enzyme localized in the mitochondrial intermembrane space that reversibly catalyzes the transfer of phosphate from ATP to creatine, forming phosphocreatine for energy shuttling to cytosol in high-demand tissues like skeletal muscle and heart. It exists as dimers or octamers, distinct from cytosolic dimeric forms, and plays a key role in the phosphocreatine/creatine shuttle that supports oxidative phosphorylation and ATP regeneration. CKMT2 shows tissue specificity for sarcomeric muscles and is essential for mitochondrial energy metabolism. In disease, it is overexpressed in colorectal cancer tissues and cell lines, correlating with adenocarcinoma pathology, larger tumors, distant metastasis, and worse survival, where it promotes tumor growth, migration, inhibits apoptosis, and enhances aerobic glycolysis via interaction with lactate dehydrogenase B (LDHB). Conversely, reduced CKMT2 expression in type 2 diabetes links to impaired muscle mitochondrial respiration, membrane potential, and glucose oxidation, independent of insulin action. Diseases like inferior myocardial infarction and dropped head syndrome are associated, though therapeutic targeting remains unexplored, with creatine as a known substrate but no direct inhibitors identified.

Other names

Creatine kinase, mitochondrial 2Mitochondrial creatine kinase 2Sarcomeric mitochondrial creatine kinase (sMtCK)SMTCK