NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial (NDUFS6)

NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial (NDUFS6) is an accessory subunit of mitochondrial complex I, the first enzyme in the electron transport chain. It is essential for the assembly and stabilization of specific subunits within complex I, supporting the transfer of electrons from NADH to ubiquinone and enabling ATP production through oxidative phosphorylation. Unlike some catalytic subunits, NDUFS6 is not directly involved in enzymatic catalysis but is critical for proper complex I function. Mutations in the NDUFS6 gene cause mitochondrial complex I deficiency, the most common primary defect in oxidative phosphorylation disorders, leading to various diseases ranging from lethal neonatal lactic acidosis to adult-onset neurodegenerative syndromes, cardiomyopathy, myopathy, and liver dysfunction. Therapeutic approaches are complicated by the essential role of this protein in energy metabolism and the genetic heterogeneity of mitochondrial disorders.

Other names

NADH:ubiquinone oxidoreductase subunit S6NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrialComplex I 13kDa subunit ACI-13kD-ACI13KDACI-13kAMC1DN9NADH-ubiquinone oxidoreductase 13 kDa-A subunit

Inhibition or modulation of mitochondrial complex I function (when complex I is targeted broadly) Restoration or amelioration of complex I deficiency-related dysfunction (in experimental therapies)