Looking Back to the Future of Mitochondrial Research

–ethos anthropoi daimon—is a famous aphorismof theGreek philosopher Heraclitus (544–483 BC). While its deeper meaning is probably more complex, the conventional translation is “a human being’s character is his/her fate.” When I was asked by George Billman to contribute my thoughts on the future of mitochondrial research it occurred to me that perhaps I could try to foretell the fate of mitochondrial research from its character, i.e., from the key themes from which the discipline developed. I will limit this brief comment to a few topics that also reflect my own interests, and that should not be considered even an attempt to be exhaustive. In the twentieth century the key issue in Bioenergetics (hence in mitochondrial research) has been the mechanism of energy conservation. The turning point was the proposal and then the demonstration of Peter Mitchell’s chemiosmotic hypothesis, i.e., that in mitochondria the basic events are the coupling of aerobic electron transfer to H+ pumping, the formation of the H+ electrochemical gradient and its harnessing by the ATP synthase (Mitchell, 1966), reprinted in Mitchell (2011). It is remarkable that the most recent advances in structural biology and superresolution microscopy, which are removing hurdles and moving the boundaries of Science beyond imagination, have confirmed the basic tenets of chemiosmotic principles in amazing detail.