期刊
CELL REPORTS
卷 33, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.108477
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资金
- Japan Society for the Promotion of Science [25111005, 18K14694]
- Exploratory Research for Advanced Technology (ERATO) from the Japan Science and Technology Agency (JST) [JPMJER1702]
- Japan Agency for Medical Research and Development [JP19gm4010005, JP18gm0710006]
- National Institutes of Health [R01NS094144]
- Grants-in-Aid for Scientific Research [18K14694] Funding Source: KAKEN
Autophagy is an intracellular degradation system, but its physiological functions in vertebrates are not yet fully understood. Here, we show that autophagy is required for inflation of air-filled organs: zebrafish swim bladder and mouse lung. In wild-type zebrafish swim bladder and mouse lung type II pulmonary epithelial cells, autophagosomes are formed and frequently fuse with lamellar bodies. The lamellar body is a lysosome-related organelle that stores a phospholipid-containing surfactant complex that lines the air-liquid interface and reduces surface tension. We find that autophagy is critical for maturation of the lamellar body. Accordingly, atg-deficient zebrafish fail to maintain their position in the water, and type-II-pneumo-cyte-specific Fip200-deficient mice show neonatal lethality with respiratory failure. Autophagy suppression does not affect synthesis of the surfactant phospholipid, suggesting that autophagy supplies lipids and membranes to lamellar bodies. These results demonstrate an evolutionarily conserved role of autophagy in lamellar body maturation.
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