Mitochondrial respiratory chain Complex I, II, III, and IV (None widely used for the group collectively; individual complexes are referred to as CI, CII, CIII, CIV.)

The mitochondrial respiratory chain consists of four principal multi-protein enzyme complexes (Complex I: NADH: ubiquinone oxidoreductase, Complex II: Succinate dehydrogenase, Complex III: Cytochrome bc1 complex, Complex IV: Cytochrome c oxidase) organized in the inner mitochondrial membrane. They facilitate the transfer of electrons from NADH and FADH2 to molecular oxygen, coupled to proton translocation that generates the electrochemical gradient required for ATP synthesis. Complexes I, III, and IV not only function individually, but also form supercomplexes (“respirasomes”) which enhance electron transport efficiency and may limit production of reactive oxygen species. Dysfunction of any complex in the chain impairs ATP synthesis and can cause a wide spectrum of diseases, making these complexes clinically important therapeutic targets. The grouping “Complex I–IV” is not a single molecule or receptor, but a functional and structural ensemble, and should be studied as individual complexes for drug discovery or mechanistic understanding.

Other names

Electron transport chain complexesMitochondrial respiratory chain complexesETC complexesOXPHOS complexes

Inhibition of electron transfer, leading to suppressed ATP production or increased ROS generation Uncoupling of proton gradient Modulation of redox state and mitochondrial signaling