PT  - JOURNAL ARTICLE
AU  - Marta Bueno
AU  - Yen-Chun Lai
AU  - Yair Romero
AU  - Judith Brands
AU  - Claudette StCroix
AU  - Catherine Corey
AU  - Jose Herazo-Maya
AU  - John Sembrant
AU  - Steve Duncan
AU  - Joseph Pelewski
AU  - Mauricio Rojas
AU  - Sruti Shiva
AU  - Charleen Chu
AU  - Ana Mora
TI  - Late-breaking abstract: Age-related PINK1 deficiency promotes mitochondria dysfuntion, epithelial injury and fibrosis in the lung
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P873
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P873.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P873.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - 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.