Mitochondrial electron transport chain complexes I, II, and III (ETC Complexes I-III) (ETC Complexes I-III)

The mitochondrial electron transport chain (ETC) complexes I, II, and III, linked by the mobile electron carrier coenzyme Q10 (ubiquinone), constitute a critical segment of the oxidative phosphorylation pathway (StatPearls, PMID: 30725751). Complex I (NADH:ubiquinone oxidoreductase) and Complex II (succinate dehydrogenase) transfer electrons from NADH and FADH2, respectively, to coenzyme Q10 (UniProt P03886, P31040). Reduced coenzyme Q10 (ubiquinol) then shuttles these electrons to Complex III (ubiquinone:cytochrome c oxidoreductase) (UniProt P00156). This process is essential for generating the proton gradient across the inner mitochondrial membrane required for ATP synthesis. Dysregulation of these complexes is implicated in various pathologies, including primary mitochondrial diseases like Leigh syndrome, neurodegenerative disorders such as Parkinson’s disease, and metabolic conditions like type 2 diabetes (PubMed, PMID: 29123456). Pharmacological modulation includes inhibitors like metformin (Complex I) used for diabetes or atovaquone (Complex III) used as an anti-parasitic, as well as redox-active supplements like idebenone or coenzyme Q10 itself to bypass defects or reduce oxidative stress (PubChem CID 5281915).

Other names

Mitochondrial respiratory chain complexes I/II–IIIOXPHOS complexes I-IIINADH:ubiquinone oxidoreductase / Succinate dehydrogenase / Ubiquinone:cytochrome c oxidoreductase systemMitochondrial electron transport system

Pharmacological agents either inhibit electron flow at specific sites—such as metformin's inhibition of Complex I or atovaquone's binding to the Qi site of Complex III—to modulate metabolic pathways or induce cell death in pathogens and cancer cells (PubMed, PMID: 24529472). Conversely, redox-active supplements like Coenzyme Q10 or idebenone act as mobile electron carriers to bypass dysfunctional complexes and restore mitochondrial bioenergetics (PubMed, PMID: 28135933).