These researchers have demonstrated that CFTR channel influences the mitophagic flux, affecting the Parkin-mediated amplify signal. In CF cells the reduction of selective degradation of altered mitochondria promoted NLRP3 inflammasome activation, worsening further the mitophagic and inflammatory response. The accumulation of dysfunctional mitochondria in CF cells promoted abnormal mtUPR activation and the recruitment of the integrated stress response, both responsible of the amplification of pro-inflammatory signals. The defects in mitophagy emerged in CF airway cells impact also on the xenophagic response, favoring the accumulation of invading bacteria.
The molecular comprehension of these sophisticated mitochondrial stress responses may contribute to define a preventive therapeutic approach focused to preserve the mitochondrial homeostasis and limit the amplification of inflammatory response.