Accumulation of damaged mitochondria in alveolar macrophages with reduced OXPHOS related gene expression in IPF.
Respir Res
; 20(1): 264, 2019 Nov 27.
Article
em En
| MEDLINE
| ID: mdl-31775876
ABSTRACT
BACKGROUND:
Impaired mitochondria homeostasis and function are established hallmarks of aging and increasing evidence suggests a link with lung fibrosis. Mitochondria homeostasis may be also affected in alveolar macrophages (AMs) in idiopathic pulmonary fibrosis (IPF). In this study, we used bronchoalveolar lavage (BAL), a tool for both clinical and research purposes, and a rich source of AMs.METHODS:
BAL samples were examined from 52 patients with IPF and 19 healthy individuals. Measurements of mitochondria reactive oxygen species (mtROS), mitochondria morphology and related gene expression were performed. Additionally, autophagy and mitophagy levels were analysed.RESULTS:
Mitochondria in AMs from IPF patients had prominent morphological defects and impaired transcription paralleled to a significant reduction of mitochondria homeostasis regulators PINK1, PARK2 and NRF1. mtROS, was significantly higher in IPF and associated with reduced expression of mitochondria-encoded oxidative phosphorylation (OXPHOS) genes. Age and decline in lung function correlated with higher mtROS levels. Augmentation of damaged, oxidised mitochondria in IPF AMs however was not coupled to increased macroautophagy and mitophagy, central processes in the maintenance of healthy mitochondria levels.CONCLUSION:
Our results suggest a perturbation of mitochondria homeostasis in alveolar macrophages in IPF.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosforilação Oxidativa
/
Proteínas Quinases
/
Macrófagos Alveolares
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Ubiquitina-Proteína Ligases
/
Fibrose Pulmonar Idiopática
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article