NADHdehydrogenase

NADH dehydrogenase, also known as NADH:quinone oxidoreductase or Complex I in mitochondria, is the first enzyme of the mitochondrial respiratory chain. It catalyzes the transfer of electrons from NADH to ubiquinone, while translocating protons across the inner mitochondrial membrane to generate a proton motive force used to synthesize ATP.

In mitochondria, Complex I is a large multi-subunit enzyme composed of a peripheral matrix arm that accepts electrons from NADH via flavin mononucleotide (FMN) and several iron-sulfur clusters, and a membrane arm that translocates protons. The initial electron acceptor is FMN; reduced FMN passes electrons through a series of iron-sulfur centers to ubiquinone, forming ubiquinol. As electrons move through the complex, conformational changes drive the translocation of protons, contributing to the electrochemical gradient. The typical stoichiometry is about four protons pumped per NADH oxidized, though exact numbers vary by organism.

NADH dehydrogenases exist in bacteria as type I (NDH-1), which are proton-pumping, and type II (NDH-2), which do not pump protons but still transfer electrons from NADH to quinone. Eukaryotes possess mitochondrial Complex I; chloroplasts and some bacteria have homologous assemblies. In humans and other animals, Complex I is essential for oxidative phosphorylation and energy production.

Inhibition and disease associations: Complex I can be inhibited by compounds such as rotenone and piericidin A. Mutations in Complex I subunits are linked to mitochondrial diseases, including Leber hereditary optic neuropathy and Leigh syndrome, and dysfunction can contribute to aging-related neurodegenerative processes through altered reactive oxygen species production.