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

2020; Cell Press; Volume: 33; Issue: 10 Linguagem: Inglês

10.1016/j.celrep.2020.108477

2639-1856

Hideaki Morishita, Yuki Kanda, Takeshi Kaizuka, Haruka Chino, Kazuki Nakao, Yoshimi Miki, Yoshitaka Taketomi, Jun‐Lin Guan, Makoto Murakami, Atsu Aiba, Noboru Mizushima,

Lipid metabolism and biosynthesis

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.