Liquidity Is a Critical Determinant for Selective Autophagy of Protein Condensates
Liquidity Is a Critical Determinant for Selective Autophagy of Protein Condensates
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DOI：
10.1016/j.molcel.2019.12.026
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发表时间：
2020-03-19
期刊：
影响因子：
16
通讯作者：
Noda, Nobuo N.
中科院分区：
文献类型：
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作者：
Yamasaki, Akinori;Alam, Jahangir Md;Noda, Nobuo N.
通过选择性自噬清除生物分子凝聚物被认为在细胞内稳态中起着至关重要的作用。然而，冷凝物的选择性自噬的机制以及流动性是否决定冷凝物对自噬降解的敏感性仍然未知。在这里，我们表明，选择性自噬货物氨肽酶I（Ape1）进行相分离，形成半液滴。Ape1特异性受体蛋白Atg19在体外和体内均定位于Ape1液滴的表面，Atg19的“漂浮性”防止其渗透到液滴中。在体外重建实验表明，Atg19和脂化Atg8是必要的和足够的选择性螯合Ape1液滴的膜。这种隔离受到Ape1液滴突变固化或Atg19漂浮能力减弱的影响。两者合计，我们建议，货物流动性和货物上存在足够量的自噬受体是至关重要的生物分子凝聚物的选择性自噬。
Clearance of biomolecular condensates by selective autophagy is thought to play a crucial role in cellular homeostasis. However, the mechanism underlying selective autophagy of condensates and whether liquidity determines a condensate's susceptibility to degradation by autophagy remain unknown. Here, we show that the selective autophagic cargo aminopeptidase I (Ape1) undergoes phase separation to form semi-liquid droplets. The Ape1-specific receptor protein Atg19 localizes to the surface of Ape1 droplets both in vitro and in vivo, with the "floatability" of Atg19 preventing its penetration into droplets. In vitro reconstitution experiments reveal that Atg19 and lipidated Atg8 are necessary and sufficient for selective sequestration of Ape1 droplets by membranes. This sequestration is impaired by mutational solidification of Ape1 droplets or diminished ability of Atg19 to float. Taken together, we propose that cargo liquidity and the presence of sufficient amounts of autophagic receptor on cargo are crucial for selective autophagy of biomolecular condensates.