Manganese regulation of COPII condensation controls circulating lipid homeostasis.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
13
04
2023
accepted:
18
09
2023
medline:
13
11
2023
pubmed:
27
10
2023
entrez:
26
10
2023
Statut:
ppublish
Résumé
Precise control of circulating lipids is instrumental in health and disease. Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation, initially via the coat protein complex II (COPII). How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. Here we report that COPII uses manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-versus-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII, and selectively controls lipoprotein secretion with a distinctive, bell-shaped function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidaemia and atherosclerosis, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.
Identifiants
pubmed: 37884645
doi: 10.1038/s41556-023-01260-3
pii: 10.1038/s41556-023-01260-3
doi:
Substances chimiques
Manganese
42Z2K6ZL8P
Lipoproteins
0
Lipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1650-1663Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 91957119
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32125021
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 91954001
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31571213
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32100947
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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