Autophagy Is Required for Maturation of Surfactant-Containing Lamellar Bodies in the Lung and Swim Bladder

• Published in: Cell reports (Cambridge) Vol. 33; no. 10; p. 108477
• Main Authors: Morishita, Hideaki, Kanda, Yuki, Kaizuka, Takeshi, Chino, Haruka, Nakao, Kazuki, Miki, Yoshimi, Taketomi, Yoshitaka, Guan, Jun-Lin, Murakami, Makoto, Aiba, Atsu, Mizushima, Noboru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.12.2020
• Subjects: autophagy; autophagy-related gene; lamellar body; lung; lysosome-related organelle; surfactant; swim bladder; lung; autophagy; lysosome-related organelle; swim bladder; autophagy-related gene; lamellar body; surfactant
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108477

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-pneumocyte-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. [Display omitted] •Autophagy is required for larval survival and swim bladder inflation in zebrafish•Autophagy is required for maturation of surfactant-containing lamellar bodies•Autophagosomes fuse with lamellar bodies in the swim bladder and lung•FIP200 in the lung is essential for neonatal survival and respiration in mice Physiological functions of macroautophagy remain not fully understood in vertebrates. Morishita et al. demonstrate that autophagy is required for inflation of air-filled organs: zebrafish swim bladder and mouse lung. In the swim bladder and type II pulmonary epithelial cells, autophagosomes fuse with lamellar bodies, which drives lamellar body maturation.