Experimental observations on the structure and function of mitochondrial complex III that are unresolved by the...

The current model of the protonmotive ubiquinone cycle as applied to mitochondrial ubiquinol-cytochrome c reductase complex (Complex III) is able to explain a number of previously puzzling observations concerning electron-transfer and proton translocating functions of the complex. However, a number of pertinent experimental observations concerning the structure and function of this complex cannot as yet be incorporated into the present version of the ubiquinone cycle. The yet unresolved problems of electron transfer uncovered by these observations include some kinetic and thermodynamic problems, uncertainties in the binding site(s) and mode of binding of ubiquinol and inhibitors, the observed multiple spectroscopic, electrochemical, and kinetic forms of cytochromes b, iron-sulfur protein, and cytochrome c1, the multiple and overlapping effects of inhibitors, and the functional role of conformational changes in the complex. It is concluded that although the Q cycle is a valuable base for the design of future experiments, its mechanism must be reconciled with the above uncertainties as well as with the accumulated evidence that Complex III can exist in two or more interchangeable forms, exhibiting different properties with respect to electron-transfer pathways, inhibitor binding, and spectral and electrochemical properties of the electron-carrier subunits.