NADH dehydrogenase (Complex I) (NDH or Complex I)

NADH dehydrogenase (Complex I) is the largest protein complex of the mitochondrial electron transport chain, containing approximately 40 polypeptide subunits organized into functional modules. This flavoprotein enzyme catalyzes the oxidation of NADH to NAD+, transferring high-energy electrons through iron-sulfur clusters to ubiquinone while simultaneously pumping protons across the inner mitochondrial membrane. This proton gradient is essential for ATP synthesis, with each NADH molecule generating approximately 2.5 ATP through chemiosmosis. Complex I is fundamental to cellular energy metabolism, as it receives electrons from glycolysis and the citric acid cycle, oxidizing eight NADH molecules per glucose molecule. Given its central role in aerobic respiration and energy production, NADH dehydrogenase is a potential target for therapeutic intervention in mitochondrial disorders and metabolic diseases, though clinical applications remain limited.

Other names

NADH oxidoreductaseNADH:ubiquinone oxidoreductaseComplex INADH dehydrogenase [ubiquinone]NDH-1 (bacterial form)NDH-2 (bacterial type II)Ndi1 (yeast NADH dehydrogenase)

Complex I catalyzes the following reaction: NADH is oxidized into NAD+, releasing a hydride ion (H-) containing two high-energy electrons and a proton. These electrons are transferred through a series of iron-sulfur clusters to ubiquinone. The energy from this electron transfer is coupled to the pumping of approximately four protons from the mitochondrial matrix into the intermembrane space. This proton gradient drives ATP synthase, producing approximately 2.5 ATP molecules per NADH molecule oxidized.