Primary cilia sense glutamine availability and respond via asparagine synthetase.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
01
09
2022
accepted:
02
02
2023
medline:
29
3
2023
pubmed:
7
3
2023
entrez:
6
3
2023
Statut:
ppublish
Résumé
Depriving cells of nutrients triggers an energetic crisis, which is resolved by metabolic rewiring and organelle reorganization. Primary cilia are microtubule-based organelles at the cell surface, capable of integrating multiple metabolic and signalling cues, but their precise sensory function is not fully understood. Here we show that primary cilia respond to nutrient availability and adjust their length via glutamine-mediated anaplerosis facilitated by asparagine synthetase (ASNS). Nutrient deprivation causes cilia elongation, mediated by reduced mitochondrial function, ATP availability and AMPK activation independently of mTORC1. Of note, glutamine removal and replenishment is necessary and sufficient to induce ciliary elongation or retraction, respectively, under nutrient stress conditions both in vivo and in vitro by restoring mitochondrial anaplerosis via ASNS-dependent glutamate generation. Ift88-mutant cells lacking cilia show reduced glutamine-dependent mitochondrial anaplerosis during metabolic stress, due to reduced expression and activity of ASNS at the base of cilia. Our data indicate a role for cilia in responding to, and possibly sensing, cellular glutamine levels via ASNS during metabolic stress.
Identifiants
pubmed: 36879119
doi: 10.1038/s42255-023-00754-6
pii: 10.1038/s42255-023-00754-6
pmc: PMC10042734
doi:
Substances chimiques
Glutamine
0RH81L854J
Aspartate-Ammonia Ligase
EC 6.3.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
385-397Informations de copyright
© 2023. The Author(s).
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