NADH:ubiquinone oxidoreductase complex assembly factor 4 (NDUFAF4)

NADH:ubiquinone oxidoreductase complex assembly factor 4 (NDUFAF4) is a nuclear-encoded mitochondrial protein essential for the assembly of mitochondrial respiratory chain complex I (NADH:ubiquinone oxidoreductase)[1][2][5]. It acts as an assembly factor, particularly associating with the Q-module during biogenesis, and is not a structural subunit of complex I itself. NDUFAF4 is required for the correct assembly and function of complex I, the first enzyme of the mitochondrial electron transport chain responsible for oxidative phosphorylation and ATP production[2]. Loss-of-function mutations in NDUFAF4 cause mitochondrial complex I deficiency, which can present clinically as Leigh syndrome and other severe mitochondrial disorders[2]. NDUFAF4 may also play a role in hormone-dependent cell proliferation and possibly in tumor cell invasion, though its primary function is complex I assembly[1]. There are currently no approved drugs targeting NDUFAF4; research into protein replacement therapies as a means to restore complex I function remains experimental[4].

Other names

NADH dehydrogenase (ubiquinone) 1 alpha subcomplex assembly factor 4NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4NADH dehydrogenase (ubiquinone) complex I, assembly factor 4Hormone-regulated proliferation-associated protein of 20 kDaHormone-regulated proliferation-associated protein, 20 kDaChromosome 6 open reading frame 66 (C6orf66)HSPC125HRPAP20MC1DN15My013bA22L21.1

Experimental TAT-ORF fusion protein can restore function by replacement of the missing assembly factor, enabling proper complex I biogenesis and function in patient-derived cells.