Q-cycle-a personal perspective

In this Minireview, I provide an overview of the developments over the period 1970 to 1990 that led to the current view of the Q-cycle mechanism of the cytochrome bc (1) complex. The perspective is necessarily personal, and places some emphasis on research on the complex in the photosynthetic bacteria, where the kinetics could be studied in situ and with better time resolution than in mitochondria. Peter Mitchell's original Q-cycle underwent several early revisions. The version of the Q-cycle currently accepted in most labs owed much to a perceptive critique by Peter Garland, who proposed a modified Q-cycle that allowed the complex to act independently. This was among several variants discussed by Mitchell in a seminal review from 1976. Six years later, despite significant advances in both mitochondrial and bacterial work, discrimination between the half-dozen or so variants that remained in active contention had proved elusive, and the kinetic data from both mitochondrial and photosynthetic systems was refractory. This was the basis of my own opposition to the Q-cycle. While trying to explain this opposition to an undergraduate student in the lab I was led to a re-evaluation of the kinetic data in the light of the substantial advances in our understanding of the biochemistry and thermodynamic properties of the complex. From this it became apparent that one version of the Q-cycle could account with satisfactory economy for the data from the photosynthetic bacteria, and for most results from work with mitochondrial complexes. The resulting model was highly constrained, and, since it incorporated Garland's suggestions for an independent mechanism, was called the modified Q-cycle. The modified Q-cycle has stood the test of time well, and the recent structural information has both confirmed the general mechanism, and allowed extension to a more detailed understanding of the molecular architecture, and the relation between structure and function.