Recently it has been demonstrated that perturbations to mitochondrial activity is sufficient to activate innate immune responses. The main objective of this project is the characterization of cardinal role of mitochondrial quality control machinery, as mitochondrial adaptation response to stress in CF may establish the inflammatory cellular susceptibility. Normally intracellular pathogens are cleared through a process called xenophagy. A similar mechanism, called mitophagy, has the cardinal role of selective degradation of altered mitochondria in stress cells, acting as mitochondrial quality control mechanism. The project will focus on three related, complementary parts aimed at obtaining a deeper insight into the relationship between xenophagy, mitochondrial quality control machineries and inflammation response induced by P. aeruginosa in CF. The first part of the project will regard the compromised xenophagy-mitophagy axis and its role in CF epithelial airways cells. The second and third part will explore the P. aeruginosa-induced mitochondrial dysfunctions in CF epithelial airways cells, and how CFTR channel influences Ca2+ signaling, in this way compromising further the mitochondrial quality control machineries.