Search for compounds able to modulate fof1 atp synthase in switching from life enzyme to cell death executor

Abstract

Mitochondria are the main site of energy power in eukaryotic cells. The enzyme FOF1 synthase is responsible for ATP production driven by the transmembrane proton gradient. The maintenance of a very low permeability of the inner mitochondrial membrane is crucial for this mechanism, since sudden opening of the permeability transition pore (PTP) leads to matrix swelling and outer membrane rupture, with release of proapoptotic factors. Recently, it has been suggested that dimers of ATP synthase in mammals could represent the main component of the mitochondrial PTP, a feature modulated by calcium and involving the matrix protein Cyclophilin D (CyPD). This study would help to develop new tools for the identification of plant secondary metabolites, in particular flavonoids, able to modulate PTP and therefore acting on the programmed cell death mediated by mitochondria. Therefore, this project would represent the first screening for plant molecules able to interfere with programmed cell death, as a preliminary study for the development of drugs active in PTPrelated pathologies.