The project aims to elucidate the relationship between mitochondrial activity and F508del-CFTR dysfunction in CF. In particular, the principal aims will be i) determine if mitochondrial impairment is the primary defect or it is secondary to GSH depletion; ii) identify the proteins and/or molecular mechanisms responsible for the reduction in GSH levels and secretion and iii) provide further information on the relationship between CFTR and mitochondria by treating FC cells with the correctors, that restore the activity of F508del-CFTR on the cell surface. Many experiments will be performed in primary CF cells, a model closer to the functional specificity of human airway cells. Understanding the molecular mechanisms responsible for the reciprocal relation between F508del-CFTR and mitochondrial bioenergetics, with respect to GSH-dependent redox imbalance, should reveal potential targets and then suggest new therapeutic strategies with the ultimate goal of a better management of the disease and relieve inflammation.