Proceedings of The Physiological Society

Mitochondria: Form and function (London, UK) (2017) Proc Physiol Soc 38, SA03

Research Symposium

The structure of the mitochondrial permeability transition pore and design of novel inhibitors

V. Giorgio2,1

1. University of Padova, Padova, Italy. 2. CNR- Neuroscience Institute, Padova, Italy.


F- ATP synthases convert the energy of the transmembrane H+ gradient into ATP with remarkable efficiency [1]. We have recently discovered that in the presence of Ca2+ F- ATP synthases can also form channels with the properties expected of the mitochondrial "permeability transition pore" (PTP) in mammals [2], yeast [3] and drosophila [4]. Ca2+-dependent PTP opening causes a large increase of permeability of the inner mitochondrial membrane, which has long been known to dissipate ion gradients and to cause detrimental effects on mitochondrial and cell function [5]. Our results show that channel activity can be seen in reconstituted systems with highly purified F- ATP synthases, indicating that channel formation must occur within the enzyme complex. I will present our recent results on the mechanism of channel formation, as studied by site directed mutagenesis of key regulatory residues of F- ATP synthases, and on the development of new inhibitors.

Where applicable, experiments conform with Society ethical requirements