NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2)

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2), also known as COXFA4L2, is a nuclear-encoded mitochondrial protein that acts as a subunit associated with the electron transport chain, particularly modulating Complex I and IV function depending on the organismal context[1][2][7]. Although originally thought to be a part of Complex I, further research revealed tissue- and context-dependent association, notably as a hypoxia-inducible subunit in certain conditions. NDUFA4L2 attenuates mitochondrial oxygen consumption, likely as a protective adaptation to low oxygen by inhibiting electron transport and reducing reactive oxygen species production. It is overexpressed in several cancers (e.g., clear cell renal cell carcinoma) and is associated with poor outcomes, contributing to a metabolic shift favoring glycolysis over oxidative phosphorylation[11]. Pathogenic variants and dysregulation are linked to multisystem mitochondrial diseases, including Leigh disease, cardiomyopathy, and neurodevelopmental disorders[2][7].

Other names

NDUFA4L2COXFA4L2NUOMSMISTRHFLJ26118NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2NDUFA4 mitochondrial complex associated like 2cytochrome c oxidase hypoxia associated subunit FA4L2NADH-ubiquinone oxidoreductase MLRQ subunit homologmitochondrial stress response hypoxia