A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
13
12
2022
accepted:
03
01
2024
medline:
18
3
2024
pubmed:
6
2
2024
entrez:
5
2
2024
Statut:
ppublish
Résumé
Cells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase networks converge on the conserved Atg1/ULK kinase complex (AKC) to induce non-selective and selective forms of autophagy in response to metabolic changes. Here we show that, upon phosphate starvation, the metabolite sensor Pho81 interacts with the adaptor subunit Atg11 at the AKC via an Atg11/FIP200 interaction motif to modulate pexophagy by virtue of its conserved phospho-metabolite sensing SPX domain. Notably, core AKC components Atg13 and Atg17 are dispensable for phosphate starvation-induced autophagy revealing significant compositional and functional plasticity of the AKC. Our data indicate that, instead of functioning as a selective autophagy receptor, Pho81 compensates for partially inactive Atg13 by promoting Atg11 phosphorylation by Atg1 critical for pexophagy during phosphate starvation. Our work shows Atg11/FIP200 adaptor subunits bind not only selective autophagy receptors but also modulator subunits that convey metabolic information directly to the AKC for autophagy regulation.
Identifiants
pubmed: 38316984
doi: 10.1038/s41556-024-01348-4
pii: 10.1038/s41556-024-01348-4
pmc: PMC10940145
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Autophagy-Related Proteins
0
Carrier Proteins
0
Transcription Factors
0
Phosphates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
366-377Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 269925409
Informations de copyright
© 2024. The Author(s).
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