Reconstitution of Autophagosomal Membrane Tethering Reveals That Atg11 Can Bind and Cluster Vesicles on Cargo Mimetics

Overview

Journal bioRxiv

Date 2024 Jan 8

PMID 38187578

Authors

Devika Andhare

Sarah Katzenell

Sarah I Najera

Katherine M Bauer

Michael J Ragusa

Affiliations

Soon will be listed here.

Abstract

Autophagy is essential for the degradation of mitochondria from yeast to humans. Mitochondrial autophagy in yeast is initiated when the selective autophagy scaffolding protein Atg11 is recruited to mitochondria through its interaction with the selective autophagy receptor Atg32. This also results in the recruitment of small 30 nm vesicles that fuse to generate the initial autophagosomal membrane. We demonstrate that Atg11 can bind to autophagosomal-like membranes in vitro in a curvature dependent manner via a predicted amphipathic helix. Deletion of the amphipathic helix from Atg11 results in a delay in the formation of mitophagy initiation sites in yeast. Furthermore, using a novel biochemical approach we demonstrate that the interaction between Atg11 and Atg32 results in the tethering of autophagosomal-like vesicles in clusters to giant unilamellar vesicles containing a lipid composition designed to mimic the outer mitochondrial membrane. Taken together our results demonstrate an important role for autophagosomal membrane binding by Atg11 in the initiation of mitochondrial autophagy.

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