Cytochrome c oxidase associated subunit FA4 (COXFA4)

Cytochrome c oxidase associated subunit FA4 (COXFA4), formerly known as NDUFA4, is a small transmembrane protein component of cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial electron transport chain, which is essential for oxidative phosphorylation and ATP generation. COXFA4 was originally thought to be a subunit of complex I, but it is now well established as a subunit of complex IV. COXFA4 is required for maximal Complex IV enzymatic activity in select cell types. Recent research has uncovered a dynamic regulation of COXFA4, where, in response to inflammation or hypoxia, it can be replaced by related proteins such as C15ORF48 via a switch regulated at both mRNA and protein levels. Loss-of-function mutations in NDUFA4 cause a mitochondrial disease resembling Leigh syndrome, marked by neuromuscular symptoms, impaired complex IV activity, and lactic acidosis. COXFA4 plays a role in regulating the assembly and function of cytochrome c oxidase and may have wider implications in inflammatory and metabolic diseases, but no drugs specifically target this subunit in clinical practice.

Other names

NDUFA4Cytochrome c oxidase subunit NDUFA4CI-MLRQMLRQCI-9kMRCAF1MISTR1Complex I-MLRQNADH-ubiquinone oxidoreductase MLRQ subunitComplex I 9kDa subunitMitochondrial respiratory chain associated factor 1Mitochondrial stress response 1NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDaNDUFA4 mitochondrial complex associatedMC4DN21

Not applicable: no selective drugs targeting COXFA4 are known. Drugs that inhibit Complex IV (such as cyanide) inhibit the whole enzyme complex, not COXFA4 individually