ACSL1 improves pulmonary fibrosis by reducing mitochondrial damage and activating PINK1/Parkin mediated mitophagy

Autor: Qi LIN, Yating LIN, Xinyan LIAO, Ziyi CHEN, Mengmeng DENG, Zhihao ZHONG
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-78136-5
Popis: Abstract Pulmonary fibrosis is a chronic interstitial lung disease with no curative therapeutic treatment, leading to significant mortality. The aims of this study were to investigate the regulatory mechanisms of mitophagy in the progression of pulmonary fibrosis. Through bioinformatics analysis, we identified the downregulation of long-chain fatty acyl-CoA synthetase 1 (ACSL1) as being associated with the severity of pulmonary fibrosis. A pulmonary fibrosis model was established through bleomycin (BLM) exposure both in vivo and in vitro. Mitoquinone (MitoQ) pretreatment significantly decreased redox damage, stabilized mitochondrial membrane potential (MMP), improved mitochondrial dynamics, and activated PINK1/Parkin-mediated mitophagy, thereby alleviating pulmonary fibrosis. In vitro, overexpression of ACSL1 mitigated mitochondrial damage and restored PINK1/Parkin-mediated mitophagy under BLM exposure. In contrast, ACSL1 inhibition exacerbated pulmonary fibrosis, and these adverse effects could not be reversed by MitoQ treatment. Taken together, our study reveals a novel mechanism underlying the pathogenesis of pulmonary fibrosis and suggests a potential therapeutic target for its treatment.
Databáze: Directory of Open Access Journals
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