@article{5fd938229fee45909c55375709fb1aba,
title = "Liquidity Is a Critical Determinant for Selective Autophagy of Protein Condensates",
abstract = "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.",
keywords = "Cvt pathway, autophagic receptor, autophagy, biomolecular condensates, floatability, liquidity, phase separation, selective autophagy",
author = "Akinori Yamasaki and Alam, {Jahangir Md} and Daisuke Noshiro and Eri Hirata and Yuko Fujioka and Kuninori Suzuki and Yoshinori Ohsumi and Noda, {Nobuo N.}",
note = "Funding Information: We thank Yuki Ishii for assistance with protein preparation, Shukun Hotta for assistance with yeast experiments, Yasuhiro Araki for providing plasmids containing the GBP sequence, Naonobu Fujita for assistance with microscope experiments, Tatsuya Kawaoka for advice on data analysis, Hidetoshi Noda and Naoya Kumagai for providing C4N4 compounds, and Alexander I. May for proofreading the manuscript. This work was supported in part by JSPS KAKENHI grants 25111004 , 18H03989 , 19H05707 (to N.N.N.), 17K18339 (to A.Y.), 19K16344 (to D.N.), 17H05894 , 17K07319 (to Y.F.), 16H06375 (to Y.O.), 16H06280 , 18H04853 (to K.S.), and 18J13429 (to E.H.); CREST , Japan Science and Technology Agency grant JPMJCR13M7 (to N.N.N.); the Takeda Science Foundation (N.N.N., Y.F., and A.Y.); the Mochida Memorial Foundation for Medical and Pharmaceutical Research (N.N.N.); the Tokyo Biochemical Research Foundation (N.N.N. and J.M.A.); and the Naito Foundation (N.N.N. and Y.F.). Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2020",
month = mar,
day = "19",
doi = "10.1016/j.molcel.2019.12.026",
language = "English",
volume = "77",
pages = "1163--1175.e9",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}