Abstract
Idiopathic Pulmonary Fibrosis (IPF) is an age-related disease. Similar to several age-related diseases that have a mitochondrial etiology, we found that alveolar type II cells (AECII) in IPF lung have marked accumulation of dysmorphic and dysfunctional mitochondria. These mitochondrial abnormalities were recapitulated in normal mice with advancing age and ER stress stimulation. We found that impaired mitochondria in IPF and aging lungs were associated with low expression of the PTEN-induced putative kinase 1 (PINK1). Knockdown of PINK1 expression in lung epithelial cells resulted in mitochondria depolarization, increase of mitochondrial mass and expression of pro-fibrotic factors. Moreover, young mice deficient in PINK1 develop similar dysmorphic dysfunctional mitochondria in the AECII and are highly vulnerable to apoptosis and development of lung fibrosis by herpesvirus infection. Our data indicates that PINK1deficiency and the subsequent mitochondria dysfunction promote fibrosis in the aging lung.
- © 2014 ERS