NADH:ubiquinone oxidoreductase complex assembly factor 8 (NDUFAF8)

NADH:ubiquinone oxidoreductase complex assembly factor 8 (NDUFAF8) is a small mitochondrial protein (74 amino acids) that plays an essential role in the *assembly of mitochondrial Complex I (NADH:ubiquinone oxidoreductase)*, a key enzyme in the oxidative phosphorylation (OXPHOS) system[1][2][3]. NDUFAF8 stabilizes the assembly factor NDUFAF5, ensuring proper Complex I biogenesis. Pathogenic bi-allelic mutations in NDUFAF8 disrupt this process, leading to severe mitochondrial disorders, most notably nuclear type mitochondrial complex I deficiency and Leigh syndrome, characterized by profound neurological impairments. NDUFAF8 belongs to the Cx9C protein family associated with mitochondrial function, and its deficiency presents as isolated Complex I deficiency in fibroblast and muscle cells, without affecting other mitochondrial complexes[1]. Currently, clinical interventions are limited to supportive care, with experimental gene repair strategies showing potential in cell models[1].

Other names

NDUFAF8C17orf89MC1DN34NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 8

Not applicable. No drugs directly targeting NDUFAF8 have defined mechanisms of action. Restoration of function has been observed in experimental systems using gene therapy or wild-type cDNA expression[1].