NADH:ubiquinone oxidoreductase complex assembly factor 6 (NDUFAF6)

NADH:ubiquinone oxidoreductase complex assembly factor 6 (NDUFAF6) is a mitochondria-localized peripheral membrane protein involved in the assembly of mitochondrial respiratory chain complex I (NADH:ubiquinone oxidoreductase), specifically by mediating incorporation of the NDUFS8 subunit into the Q module at early stages of complex I biogenesis[1][2][3][4][5][6][7][8]. It acts as a *pseudoenzyme* with a structurally vestigial active site and contains a predicted phytoene synthase domain, but evolutionary analysis indicates it does not retain canonical enzyme activity[1][6]. Pathogenic biallelic mutations in NDUFAF6 are linked to *complex I deficiency* syndromes, such as Leigh syndrome—a progressive neurodegenerative disorder—and Acadian variant Fanconi syndrome, affecting mitochondrial energy metabolism[2][3][8]. NDUFAF6 does not serve as the direct target of any approved drugs, but modulation of related assembly factors or subunits represents a potential therapeutic avenue for mitochondrial disorders due to NDUFAF6 dysfunction[1].

Other names

C8orf38lncRESTMGC40214Putative phytoene synthaseFRTS5MC1DN17UPF0551 protein C8orf38, mitochondrialNADH dehydrogenase (ubiquinone) complex I, assembly factor 6

Not directly drug-targeted; functional restoration strategies include *overexpression* of the NDUFS8 subunit to bypass NDUFAF6 deficiency[1].