NADH:ubiquinone oxidoreductase subunit S7 (NDUFS7) (NDUFS7)

Mitochondrial Complex I, specifically the PSST subunit-associated site, is a critical component of the mitochondrial electron transport chain responsible for the oxidation of NADH and the reduction of ubiquinone (UniProt: P48764). The PSST subunit (NDUFS7) is a core, highly conserved protein that contributes to the formation of the ubiquinone-binding pocket (Q-site) and houses the N2 iron-sulfur cluster, the final electron donor in the complex's electron transfer chain (PubMed: 15544951). In the context of viable cardiomyocytes, this site is a key target for pharmacological intervention to mitigate ischemia-reperfusion injury by reducing the burst of reactive oxygen species (ROS) upon reperfusion (PubMed: 22303013). Drugs like metformin are thought to interact with this region to mildly and reversibly inhibit complex I activity, which provides cardioprotective effects and activates the AMPK pathway (PubMed: 24509906). Beyond cardioprotection, the PSST subunit is clinically significant as mutations in the NDUFS7 gene are a known cause of Leigh syndrome, a severe neurodegenerative disorder characterized by mitochondrial dysfunction (PubMed: 11431143). This site is also the target of classic inhibitors such as rotenone and piericidin A, which are used extensively in biochemical research to study mitochondrial respiration.

Other names

PSST subunitMitochondrial complex I PSST subunitNADH dehydrogenase [ubiquinone] iron-sulfur protein 7CI-PSSTComplex I-7 (CI-7)

Reversible inhibition of the ubiquinone-binding site (Q-site) of Mitochondrial Complex I, which prevents the transfer of electrons from the N2 iron-sulfur cluster to ubiquinone, thereby modulating the proton motive force and reducing the production of reactive oxygen species.