Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and autophagy.
ER-phagy
UFMylation
phylogenomics
ribosome stalling
selective autophagy
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 05 2023
15 05 2023
Historique:
revised:
12
01
2023
received:
06
07
2022
accepted:
18
01
2023
medline:
16
5
2023
pubmed:
11
2
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
UFMylation involves the covalent modification of substrate proteins with UFM1 (Ubiquitin-fold modifier 1) and is important for maintaining ER homeostasis. Stalled translation triggers the UFMylation of ER-bound ribosomes and activates C53-mediated autophagy to clear toxic polypeptides. C53 contains noncanonical shuffled ATG8-interacting motifs (sAIMs) that are essential for ATG8 interaction and autophagy initiation. However, the mechanistic basis of sAIM-mediated ATG8 interaction remains unknown. Here, we show that C53 and sAIMs are conserved across eukaryotes but secondarily lost in fungi and various algal lineages. Biochemical assays showed that the unicellular alga Chlamydomonas reinhardtii has a functional UFMylation pathway, refuting the assumption that UFMylation is linked to multicellularity. Comparative structural analyses revealed that both UFM1 and ATG8 bind sAIMs in C53, but in a distinct way. Conversion of sAIMs into canonical AIMs impaired binding of C53 to UFM1, while strengthening ATG8 binding. Increased ATG8 binding led to the autoactivation of the C53 pathway and sensitization of Arabidopsis thaliana to ER stress. Altogether, our findings reveal an ancestral role of sAIMs in UFMylation-dependent fine-tuning of C53-mediated autophagy activation.
Identifiants
pubmed: 36762703
doi: 10.15252/embj.2022112053
pmc: PMC10183829
doi:
Substances chimiques
Proteins
0
Peptides
0
Autophagy-Related Protein 8 Family
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e112053Subventions
Organisme : Medical Research Council
ID : MR/T020970/1
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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