NADH:ubiquinone oxidoreductase (Complex I) (Complex I)

NADH:ubiquinone oxidoreductase, commonly known as Mitochondrial Complex I, is the largest and first enzyme of the mitochondrial respiratory chain [2, 10]. It plays a critical role in cellular energy production by coupling the transfer of electrons from NADH to ubiquinone with the translocation of protons across the inner mitochondrial membrane, thereby contributing to the proton motive force for ATP synthesis [15, 18]. The complex contains several essential iron-sulfur (Fe-S) clusters (e.g., N1a, N1b, N2, N3, N4, N5, N6a, N6b) that facilitate electron relay through core subunits such as NDUFS1, NDUFS7, and NDUFV1 [5, 16]. Dysfunctions in Complex I or its Fe-S subunits are linked to various pathologies, including primary mitochondrial disorders like Leigh syndrome and neurodegenerative diseases like Parkinson's disease [10, 11]. Therapeutically, Complex I is targeted by drugs like metformin for metabolic regulation and is being explored as a target for cancer therapy to exploit metabolic vulnerabilities [2, 13].

Other names

NADH dehydrogenaseNADH-coenzyme Q oxidoreductaseMitochondrial respiratory chain complex IType I NADH dehydrogenaseNDUFS1NDUFS2NDUFS7NDUFS8NDUFV1NDUFV2

Inhibition of NADH oxidation and electron transfer to ubiquinone, leading to modulation of the NAD+/NADH ratio, reduction in ATP synthesis, and activation of AMPK signaling [2, 10, 15].