NADH:ubiquinone oxidoreductase (mitochondrial respiratory chain complex I) (Complex I or CI)

NADH:ubiquinone oxidoreductase (complex I) is the largest and first enzyme complex of the mitochondrial electron transport chain, composed of 44–45 subunits encoded by both nuclear and mitochondrial genomes[2][6]. It catalyzes the electron transfer from NADH to ubiquinone (coenzyme Q) and couples this redox reaction to proton translocation across the inner mitochondrial membrane, generating a proton-motive force that drives ATP synthesis by ATP synthase[1][4][5]. Complex I is L-shaped, with a peripheral catalytic arm protruding into the mitochondrial matrix and a membrane arm embedded within the inner membrane, hosting proton translocation channels[2][4]. Dysfunction of complex I is associated with various human diseases, including mitochondrial encephalomyopathy, neurodegenerative diseases like Parkinson’s and Alzheimer’s, cardiovascular diseases, and some cancers[1][3][6]. Given its central role in cellular metabolism, complex I is both a therapeutic target and a site of toxicity for several drugs and environmental toxins.

Other names

Mitochondrial complex IMitochondrial OXPHOS complex INADH:ubiquinone oxidoreductaseNADH dehydrogenase (ubiquinone)Electron transport chain complex I

- **Inhibition of electron transfer:** Many small molecule inhibitors (e.g., rotenone, piericidin A) block the transfer of electrons from NADH to ubiquinone, disrupting ATP production and increasing reactive oxygen species formation[5]. - **Modulation of proton translocation:** Inhibitors and genetic defects can impair the ability of complex I to pump protons, collapsing the mitochondrial membrane potential[5][4]. - **Activation of reverse electron transport:** Under high proton-motive force, electrons can flow in reverse, contributing to oxidative stress and pathological conditions[5].