Mitochondrial electron transport chain complexes I–III (ETC Complexes I–III)

The mitochondrial electron transport chain (ETC) complexes I–III are essential protein assemblies located within the inner mitochondrial membrane that facilitate the transfer of electrons from metabolic substrates to oxygen (Wikipedia, 2026; UBCO, 2026). Complex I (NADH:ubiquinone oxidoreductase) and Complex II (succinate dehydrogenase) initiate this process by oxidizing NADH and FADH2, respectively, and transferring electrons to the mobile carrier ubiquinone (PMC, 2021; Frontiers, 2021). Complex III (ubiquinol-cytochrome c oxidoreductase) then transfers these electrons to cytochrome c, a process coupled with the translocation of protons across the membrane to generate the electrochemical gradient necessary for ATP synthesis (Patsnap, 2024). Beyond energy production, these complexes are the primary cellular sites for reactive oxygen species (ROS) generation, which plays a dual role in signaling and oxidative damage (PubMed, 2011; PMC, 2021). Therapeutically, inhibitors of these complexes are being explored as mitocans to selectively induce apoptosis in cancer cells by disrupting their metabolic adaptation (ResearchGate, 2021). However, because of their central role in systemic energy metabolism, targeting these complexes requires careful management to avoid severe side effects such as lactic acidosis and neurotoxicity (PMC, 2011; SCBT, 2024).

Other names

Mitochondrial respiratory chain complexes I–IIIOXPHOS complexes I–IIIRespiratory chain complexes I–IIIMitochondrial complexes I, II, and III

Inhibition of electron transfer within the respiratory chain, leading to decreased ATP production and increased reactive oxygen species (ROS) generation.