Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 Apr 2024
03 Apr 2024
Historique:
received:
24
02
2023
accepted:
19
03
2024
medline:
4
4
2024
pubmed:
4
4
2024
entrez:
3
4
2024
Statut:
epublish
Résumé
Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.
Identifiants
pubmed: 38570500
doi: 10.1038/s41467-024-47095-w
pii: 10.1038/s41467-024-47095-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2859Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82170671
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82172585
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81770648
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81972286
Organisme : Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)
ID : 2018A030313259
Organisme : Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)
ID : 2015A030312013
Informations de copyright
© 2024. The Author(s).
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