Liquidity Is a Critical Determinant for Selective Autophagy of Protein Condensates

Akinori Yamasaki, Jahangir Md Alam, Daisuke Noshiro, Eri Hirata, Yuko Fujioka, Kuninori Suzuki, Yoshinori Ohsumi, Nobuo N. Noda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1163-1175.e9
JournalMolecular Cell
Volume77
Issue number6
DOIs
Publication statusPublished - 2020 Mar 19
Externally publishedYes

Keywords

  • Cvt pathway
  • autophagic receptor
  • autophagy
  • biomolecular condensates
  • floatability
  • liquidity
  • phase separation
  • selective autophagy

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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