Understanding the Cytochrome Bc Complexes by What They Don't Do. The Q-cycle at 30

The cytochrome (cyt) bc(1), b(6)f and related complexes are central components of the respiratory and photosynthetic electron transport chains. These complexes carry out an extraordinary sequence of electron and proton transfer reactions that conserve redox energy in the form of a trans-membrane proton motive force for use in synthesizing ATP and other processes. Thirty years ago, Peter Mitchell proposed a general turnover mechanism for these complexes, which he called the Q-cycle. Since that time, many opposing schemes have challenged the Q-cycle but, with the accumulation of large amounts of biochemical, kinetic, thermodynamic and high-resolution structural data, the Q-cycle has triumphed as the accepted model, although some of the intermediate steps are poorly understood and still controversial. One of the major research questions concerning the cyt bc(1) and b(6)f complexes is how these enzymes suppress deleterious and dissipative side reactions. In particular, most Q-cycle models involve reactive semiquinone radical intermediates that can reduce O(2) to superoxide and lead to cellular oxidative stress. Current models to explain the avoidance of side reactions involve unprecedented or unusual enzyme mechanisms, the testing of which will involve new theoretical and experimental approaches.