Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial (ALKBH7)

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial (ALKBH7), is a mitochondrial enzyme within the AlkB family that catalyzes oxidative reactions using alpha-ketoglutarate as a co-substrate. Unlike other AlkB family members that primarily target nucleic acids, ALKBH7 appears to act mainly on protein or mitochondrial RNA substrates. It is essential for alkylation- and oxidation-induced programmed necrosis, acting as a pro-death factor by triggering mitochondrial membrane potential collapse and mitochondrial dysfunction, leading to energy depletion and cell death. ALKBH7 regulates the demethylation of certain RNA modifications (e.g., m²²G, m¹A) in mitochondrial tRNAs, thereby affecting mitochondrial RNA processing, translation, and activity. Deficiency in ALKBH7 protects cells from DNA alkylation-induced cell death but causes increased body fat and altered metabolic regulation, suggesting roles in fatty acid metabolism and energy homeostasis. ALKBH7 has also been implicated in the regulation of dialdehyde (glyoxal/methylglyoxal) metabolism in the heart, impacting the tissue’s resilience to ischemia-reperfusion stress. In cancer, genetic alterations and expression patterns of ALKBH7 are linked to prostate cancer and pan-cancer prognosis. While the physiological substrate and direct drug interactions remain unclear, ALKBH7 is considered a potential therapeutic target in cancer, necrosis-associated diseases, and metabolic syndromes.

Other names

ALKBH7alkB homolog 7ABH7SPATA11spermatogenesis-associated protein 11alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrialalkylated DNA repair protein alkB homolog 7spermatogenesis cell proliferation-related proteinMGC10974UNQ6002/PRO34564UNQ6002