Electron Transport Chain
A series of protein complexes in the inner mitochondrial membrane that transfer electrons through a series of redox reactions, generating the proton gradient that drives ATP synthesis. Cardiolipin is essential for organising these complexes. Elamipretide improves electron transport chain function in Barth syndrome.
Technical Context
ETC complexes: Complex I (NADH dehydrogenase, 45 subunits, ~1000kDa — oxidises NADH, pumps 4H⁺), Complex II (succinate dehydrogenase, 4 subunits — oxidises FADH₂, no proton pumping), Complex III (cytochrome bc1, 11 subunits — transfers electrons from CoQ to cytochrome c, pumps 4H⁺ via Q-cycle), Complex IV (cytochrome c oxidase, 13 subunits — transfers electrons to O₂ producing H₂O, pumps 2H⁺), and Complex V (ATP synthase, ~17 subunits — uses proton gradient to synthesise ATP via rotary catalysis, approximately 3H⁺ per ATP). Supercomplex organisation: CI+CIII₂+CIV forms the respirasome, optimising electron transfer and reducing ROS. Cardiolipin fills the supercomplex interfaces. In Barth syndrome, abnormal cardiolipin disrupts supercomplex assembly → electrons leak → superoxide production increases → oxidative damage compounds the ATP deficit. Elamipretide's cardiolipin stabilisation improves supercomplex organisation and reduces electron leak.