Language
English
Publication Date
2-1-2024
Journal
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI
10.1016/j.bbadis.2023.166960
PMID
37979225
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease of unknown etiology. The emerging evidence demonstrates that metabolic homeostatic imbalance caused by repetitive injuries of the alveolar epithelium is the potential pathogenesis of IPF. Proteomic analysis identified that Acetyl-CoA synthetase short chain family member 3 (ACSS3) expression was decreased in IPF patients and mice with bleomycin-induced fibrosis. ACSS3 participated in lipid and carbohydrate metabolism. Increased expression of ACSS3 downregulated carnitine palmitoyltransferase 1A (CPT-1A) and resulted in the accumulation of lipid droplets, while enhanced glycolysis which led to an increase in extracellular lactic acid levels in A549 cells. ACSS3 increases the production of succinyl-CoA through propionic acid metabolism, and decreases the generation of acetyl-CoA and ATP in alveolar epithelial cells. Overexpression of Acss3 inhibited the excessive deposition of ECM and attenuated the ground-glass opacity which determined by micro-CT in vivo. In a nutshell, our findings demonstrate that ACSS3 decreased the fatty acid oxidation through CPT1A deficiency and enhanced anaerobic glycolysis, this metabolic reprogramming deactivate the alveolar epithelial cells by lessen mitochondrial fission and fusion, increase of ROS production, suppression of mitophagy, promotion of apoptosis, suggesting that ACSS3 might be potential therapeutic target in pulmonary fibrosis.
Keywords
Animals, Humans, Mice, Acetyl Coenzyme A, Epithelial Cells, Homeostasis, Proteomics, Pulmonary Fibrosis, Acetate-CoA Ligase, ACSS3, Metabolic reprogramming, Mitochondrial dysfunction, Pulmonary fibrosis, Lung Diseases, Interstitial; Metabolomics; Pulmonary Emphysema; Tomography, X-Ray Computed; Cross-Sectional Studies
Published Open-Access
yes
Recommended Citation
Wang, Lan; Yuan, Hongmei; Li, Wenwen; et al., "ACSS3 Regulates the Metabolic Homeostasis of Epithelial Cells and Alleviates Pulmonary Fibrosis" (2024). Faculty, Staff and Students Publications. 6785.
https://digitalcommons.library.tmc.edu/baylor_docs/6785