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Updated: May 1, 2026
Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
Cargo binding to Atg19 unmasks additional Atg8 binding sites to mediate membrane-cargo apposition during selective
Justyna Sawa-Makarska1, Christine Abert1, Julia Romanov1
1Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Abstract:
Autophagy protects cells from harmful substances such as protein aggregates, damaged mitochondria and intracellular pathogens, and has been implicated in a variety of diseases. Selectivity of autophagic processes is mediated by cargo receptors that link cargo to Atg8 family proteins on the developing autophagosomal membrane. To avoid collateral degradation during constitutive autophagic pathways, the autophagic machinery must not only select cargo but also exclude non-cargo material. Here we show that cargo directly activates the cargo receptor Atg19 by exposing multiple Atg8 binding sites. Furthermore, Atg19 mediates tight apposition of the cargo and Atg8-coated membranes in a fully reconstituted system. These properties are essential for the function of Atg19 during selective autophagy in vivo. Our results suggest that cargo receptors contribute to tight membrane bending of the isolation membrane around the cargo.
Insights
Cargo receptors like Atg19 activate selective autophagy by exposing binding sites, ensuring proper cargo targeting and membrane bending for cellular cleanup. This mechanism prevents unwanted degradation in essential cellular processes.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Autophagy is a crucial cellular process for degrading damaged components and pathogens.
- Selective autophagy relies on cargo receptors to link specific targets to the autophagosome.
- Preventing degradation of non-target materials is vital for cellular homeostasis.
Purpose of the Study:
- To investigate the mechanism by which cargo receptors mediate selective autophagy.
- To elucidate the role of cargo activation in the autophagic pathway.
- To understand how cargo receptors ensure cargo specificity and membrane interactions.
Main Methods:
- In vitro reconstitution assays.
- Analysis of cargo receptor Atg19 binding and activation.
- In vivo studies of selective autophagy in yeast models.
Main Results:
- Cargo directly activates the cargo receptor Atg19, revealing multiple Atg8 binding sites.
- Atg19 facilitates close membrane apposition between cargo and the autophagosomal membrane.
- These functions of Atg19 are essential for selective autophagy in vivo.
Conclusions:
- Cargo receptors play a critical role in the specificity and efficiency of selective autophagy.
- Cargo-induced activation of receptors is key for recruiting the autophagic machinery.
- Selective autophagy receptors contribute to the membrane bending required for autophagosome formation around cargo.
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