depositphotos_137014128-stock-illustration-user-profile-icon.jpg Supervisore: Prof.ssa Lippe
Mitochondrial F-ATP synthase-CyPD complex and its involvement in the opening of the permeability transition pore
Cyclophilin D (CyPD) is a protein localized in mitochondrial matrix. It’s involved in the generation of the mitochondrial permeability transition pore (PTP), a Ca2+-dependent, unselective channel involved in mediating fast Ca2+release from mitochondria (short open times) and in generating a bioenergetic failure eventually leading to cell death (long open times). It has been demonstrated that a key event in PTP formation is the CyPD interaction with the OSCP subunit of ATP synthase, one of the most promising candidate as the PTP. The main objective of my project is to study the molecular mechanisms underlying the transition of ATP synthase to PTP mediated by CyPD and by a N-terminally truncated form of CyPD, which has been recently identified in my laboratory group. Biochemical, biophysical and cell-based approaches will be used. Recombinant CyPD and its variants will be produced and their ability to interact with OSCP and induce PTP formation will be evaluated in vitro experiments. These variants will be re-expressed in different cellular models lacking endogenous CyPD to assess their effects on the functionality of PTP and eventually cell survival. PTP opening is a detrimental event in mitochondrial transplantation, which is an emerging strategy for the treatment of mitochondrial diseases, as well as of several metabolic and neurological disorders. An additional goal of my studies will be to investigate the possible role of CyPD in negatively affecting the success of mitochondrial transplantation.