Active proton leak in mitochondria: A new way to regulate substrate oxidation

The main function of mitochondria is energy transduction, from substrate oxidation to the free energy of ATP synthesis, through oxidative phosphorylation. For physiological reasons, the degree of coupling between these two processes must be modulated in order to adapt redox potential and ATP turnover to cellular needs. Such a modulation leads to energy wastage. To this day, two energy wastage mechanisms have been described: the membrane passive proton conductance (proton leak) and the decrease in the coupling efficiency between electrons transfer and proton extrusion at the proton pumps level (redox or proton slipping). In this paper, we describe a new energy wastage mechanism of interest. We show that in isolated yeast mitochondria, the membrane proton conductance is strictly dependent on the external dehydrogenases activity. An increase in their activity leads to an increase in the membrane proton conductance. This proton permeability is independent of the respiratory chain and ATP synthase proton pumps. We propose to name this new mechanism “active proton leak.” Such a mechanism could allow a wide modulation of substrate oxidation in response to cellular redox constraints.