Forty years of Mitchell's proton circuit: From little grey books to little grey cells.

It is more than forty years since Peter Mitchell published his first 'little grey book' laying out his chemiosmotic hypothesis. Although ideas about the molecular mechanisms of the proton pumps have evolved considerably since then, his concept of 'coupling through proton circuits' remains remarkably prescient, and has provided the inspiration for the research careers of this author and many others. This review is a personal account of how the proton circuit has been followed from the little grey book, via brown fat and calcium transport to investigations into the life and death of neurons, Hercule Poirot's 'little grey cells'.