NADH:ubiquinone oxidoreductase subunit AB1 (NDUFAB1)

NADH:ubiquinone oxidoreductase subunit AB1 (NDUFAB1) is a mitochondrial acyl carrier protein and an accessory, non-catalytic subunit of Complex I (NADH dehydrogenase) in the mitochondrial electron transport chain[1][3][4]. The protein is encoded on chromosome 16p12.2 and consists of 156 amino acids, forming an L-shaped structure with both hydrophobic transmembrane and hydrophilic peripheral arm domains[1][3]. NDUFAB1 is critical in cellular respiration, acting as an anchor for complex I and participating in electron transfer from NADH to ubiquinone[3][4]. Beyond its structural role, it coordinates the assembly and stability of mitochondrial respiratory complexes and supercomplexes by regulating iron-sulfur cluster biosynthesis, contributing to energy production and limiting pathologic ROS emission[2]. It also functions as a carrier for growing fatty acid chains, and participates in iron-sulfur cluster biogenesis, which is essential for the activity of many mitochondrial enzymes[1][5][6]. Cardiac-specific deficiency leads to severe mitochondrial dysfunction, increased ROS, dilated cardiomyopathy, and heart failure in animal models, highlighting its essential role in mitochondrial health and function[2]. It is associated with genetic risk for anxiety disorders and congenital heart defects such as Tetralogy of Fallot[3]. NDUFAB1 is widely conserved and indispensable for cell viability in some cell types[7]. No approved drugs directly target NDUFAB1, but modulation represents a promising therapeutic strategy for mitochondrial diseases and heart failure[2][3].

Other names

Acyl carrier protein, mitochondrialACPACP1SDAPFASN2ACI-SDAPNADH-ubiquinone oxidoreductase 9.6 kDa subunitcomplex I SDAP subunitNADH dehydrogenase (ubiquinone) 1 alpha/beta subcomplex 1mitochondrial acyl carrier protein

Current evidence suggests therapeutic intervention would act by modulating assembly/function of electron transport chain complexes, enhancing mitochondrial bioenergetics, or limiting ROS production