Autophagy Is Required for Maturation of Surfactant-Containing Lamellar Bodies in the Lung and Swim Bladder.
Autophagy Is Required for Maturation of Surfactant-Containing Lamellar Bodies in the Lung and Swim Bladder.
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DOI：
10.1016/j.celrep.2020.108477
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发表时间：
2020-12-08
期刊：
影响因子：
8.8
通讯作者：
Mizushima N
中科院分区：
文献类型：
--
作者：
Morishita H;Kanda Y;Kaizuka T;Chino H;Nakao K;Miki Y;Taketomi Y;Guan JL;Murakami M;Aiba A;Mizushima N
自噬是一种细胞内降解系统，但其在脊椎动物中的生理功能尚不完全清楚。在这里，我们发现自噬是充气器官膨胀所必需的：斑马鱼的鱼鳔和小鼠的肺。在野生型斑马鱼鱼鳔和小鼠肺II型肺上皮细胞中，自噬体形成并经常与板层体融合。片层体是溶酶体相关的细胞器，它储存了一种含磷脂的表面活性剂复合物，这种复合物排列在气液界面上，降低了表面张力。我们发现自噬对板层体的成熟至关重要。因此，缺乏atg的斑马鱼不能在水中保持位置，ii型肺细胞特异性缺乏fip200的小鼠表现出新生儿呼吸衰竭的致命性。自噬抑制不影响表面活性剂磷脂的合成，提示自噬为层状体提供脂质和膜。这些结果表明自噬在板层体成熟过程中具有进化保守的作用。脊椎动物巨噬的生理功能尚不完全清楚。Morishita等人证明，自噬是充气器官（斑马鱼的鱼鳔和小鼠的肺）膨胀所必需的。在鱼鳔和II型肺上皮细胞中，自噬体与板层体融合，推动板层体成熟。
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 lyso-some-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. 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.
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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
10.5
作者：
Chen S;Wang C;Yeo S;Liang CC;Okamoto T;Sun S;Wen J;Guan JL
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Guan JL
影响因子：
4
作者：
Fazeli G;Trinkwalder M;Irmisch L;Wehman AM
通讯作者：
Wehman AM
影响因子：
6.5
作者：
Fitzgerald, Michael L.;Xavier, Ramnik;Freeman, Mason W.
通讯作者：
Freeman, Mason W.
斑马鱼游泳鳔表面活性剂系统的发育和溶酶体相关细胞器的生物发生受 BLOS1 调节。
影响因子：
3.3
作者：
Chen, Tianbing;Song, Guili;Huang, Kaiyao
通讯作者：
Huang, Kaiyao