Abstract
Mitophagy is the selective digestion of damaged mitochondria. Mitochondria dysfunction and impaired mitophagy in AECIIs may play a role in the pathogenesis of IPF. PINK1 is a major regulator of mitophagy, while PINK1 deficiency promotes the accumulation of dysfunctional mitochondria in AECIIs in IPF. There have been no studies to date evaluating mitophagy in macrophages in IPF. However, an autophagy defect in alveolar macrophages of smokers resulting in mitochondrial dysfunction has been demonstrated. The purpose of this study was the evaluation of mitochondrial homeostasis in BALF cells in IPF and RA-ILD. 55 IPF patients, 20 healthy controls and 23 RA-ILD patients were included in the study. We tested the expression of AKT3, a major regulator of mitochondria homeostasis. AKT3 was up-regulated in RA-ILD versus IPF patients. Furthermore, we observed a significant down-regulation of PINK1 in IPF and RA-ILD patients versus controls. Interestingly, PINK1 and AKT3 expression positively correlated only in IPF but not in RA patients. Autophagy levels were also analysed through the expression of Beclin1, p62 and LC3. A positive correlation for all groups was demonstrated between AKT3 and p62 as well as between PINK1 and p62 in IPF. A trend for lower levels of p62 protein in IPF patients versus controls was indicated by Western Blot. LC3B levels tended to be higher in IPF versus control. Moreover, mitosox analysis was performed in order to define the oxidative status of macrophages and hence the levels of mitochondrial dysfunction in fibrotic disorders. Our results demonstrate changes in the mitophagy status in IPF macrophages relative to control and RA-ILD patients.
- Copyright ©ERS 2015