Supramolecular Organization of the Respiratory Chain

The transmembrane protein complexes of the respiratory chain generate an electrochemical gradient over the mitochondrial inner membrane and the bacterial plasma membrane. Electrons are transferred from NADH via complex I (NADH: ubiquinone oxidoreductase) and ubiquinone to complex III (ubiquinol:cytochrome c oxidoreductase) and via the peripheral electron carrier cytochrome c and complex IV (cytochrome c oxidase) to the terminal acceptor, molecular oxygen. The electrochemical proton gradient is used by F1F o -ATP synthase to produce ATP. The classical model of the respiratory chain envisions these complexes diffusing freely in the membrane and electron transfer occurring by random collision. This model is increasingly being challenged by studies that indicate a high level of orga- nization of the protein complexes. After membrane solubilisation with mild detergents, supercomplexes with various combinations of complex I, III and IV and dimers of ATP synthase can be isolated. Electron microscopic studies have con fi rmed that these supercomplexes have a distinct architecture. A 3D reconstruction of a supercomplex from bovine heart mitochondria has shown that the ubiquinone and cytochrome c binding sites of the different complexes face each other, suggesting a role in substrate channeling. Formation of supercomplexes has also been shown to play a role in the assembly and stability of the complexes, especially complex I, suggesting that they constitute the functional state of the respiratory chain. Whereas the ATP synthase dimers in mitochondria were shown to form ribbons and appear to shape the cristae membranes, a higher-order organization of complexes I, III and IV has not yet been demonstrated