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Mitochondria Homeostasis Plays a Key Role in the Age‐related Susceptibility to Lung Epithelial Injury and Fibrosis
Author(s) -
Bueno Marta,
Lai YenChu,
Romero Yair,
Brands Judith,
St. Croix Claudette,
Rojas Mauricio,
Shiva Sruti,
Chu Charleen,
Mora Ana
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1015.3
Subject(s) - pink1 , mitophagy , mitochondrion , idiopathic pulmonary fibrosis , lung , medicine , fibrosis , pulmonary fibrosis , cancer research , pathology , biology , apoptosis , autophagy , microbiology and biotechnology , genetics
Rationale Aging is associated with increased susceptibility to lung pathologies. The prevalence of idiopathic pulmonary fibrosis (IPF) has been found to increase with age. While familial disease has been related to disordered telomerase activity and mutations of SPC, the effects of advancing age and lung epithelium dysfunction and fibrosis remains unclear. Methods Lung fibrosis and mitochondria function, morphology and dynamics were analyzed in alveolar epithelial cell type II (AECII) of patients with IPF, aging mice and mice deficient in PINK1 (PTEN‐induced putative kinase 1). Results We found that 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 PINK1. Knockdown of PINK1 expression in lung epithelial cells resulted in mitochondria depolarization, 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. Conclusion Our data indicates that PINK1 deficiency and the subsequent swollen mitochondria dysfunction in the presence of ER stress causes defective mitophagy and promotion of fibrosis in the aging lung.