A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits
Journal
Molecular Cell
Journal Volume
80
Journal Issue
5
Pages
764-778.e7
Date Issued
2020-12
Author(s)
Florian Wilfling
Philipp S. Erdmann
Yumei Zheng
Dawafuti Sherpa
Stefan Jentsch
Boris Pfander
Brenda A. Schulman
Wolfgang Baumeister
Abstract
Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargo to the membrane-bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we report a selective autophagy pathway for protein condensates formed by endocytic proteins in yeast. In this pathway, the endocytic 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 and 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 route. Our data suggest a model for autophagic degradation of macromolecular protein complexes by the action of intrinsic autophagy receptors.
Subjects
Atg11; Atg8; Ede1; clathrin-mediated endocytosis; intrinsic autophagy receptor; liquid-liquid phase separation; selective autophagy
Publisher
Elsevier {BV}
Type
journal article