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A selective autophagy pathway for phase separated endocytic protein deposits

By Florian Wilfling, Chia-Wei Lee, Philipp S Erdmann, Yumei Zheng, Stefan Jentsch, Boris Pfander, Brenda A Schulman, Wolfgang Baumeister

Posted 26 May 2020
bioRxiv DOI: 10.1101/2020.05.26.116368

Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargoes to the membrane bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we discover a selective autophagy pathway for protein condensates formed by endocytic proteins. In this pathway, the endocytic yeast protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis, does not involve other known selective autophagy receptors, but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates - at the plasma membrane and in autophagic bodies - shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy pathway. Our data suggest a model for autophagic degradation of membraneless compartments by the action of intrinsic autophagy receptors. ### Competing Interest Statement The authors have declared no competing interest.

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