Supervisore: Prof.ssa Corazza

Structural studies of the interaction between cyclophilin D (CyPD) and the OSCP subunit of the mitochondrial FOF1 ATP synthase and its role in the modulation of the permeability transition pore

The mitochondrial permeability transition (PT) has been studied for more than four decades. While its physiological and pathological roles have been mostly established, its molecular nature has remained elusive and a matter of discussion for years. The finding that Cyclophilin D (CyPD), the most important PT regulator, binds to the lateral stalk of F-ATP Synthase set the basis for a new theory according to which the enzymatic complex could be the molecular entity behind PT. Our study aims to define the structural features of the interaction between CyPD and OSCP, the most likely binding partner of CyPD on F-ATP Synthase. This will be carried out adopting nuclear magnetic resonance (NMR) spectroscopy. NMR allows to determine the structural features of the interaction between two partners in solution at an atomic level, which potentially will set the basis for future drug-design for the modulation of the PT in pathological conditions.