1-Deoxydihydroceramide causes anoxic death by impairing chaperonin-mediated protein folding.

Détails

ID Serval
serval:BIB_62B2442C63AD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
1-Deoxydihydroceramide causes anoxic death by impairing chaperonin-mediated protein folding.
Périodique
Nature metabolism
Auteur(s)
Hannich J.T., Haribowo A.G., Gentina S., Paillard M., Gomez L., Pillot B., Thibault H., Abegg D., Guex N., Zumbuehl A., Adibekian A., Ovize M., Martinou J.C., Riezman H.
ISSN
2522-5812 (Electronic)
ISSN-L
2522-5812
Statut éditorial
Publié
Date de publication
10/2019
Peer-reviewed
Oui
Volume
1
Numéro
10
Pages
996-1008
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Ischaemic heart disease and stroke are the most common causes of death worldwide. Anoxia, defined as the lack of oxygen, is commonly seen in both these pathologies and triggers profound metabolic and cellular changes. Sphingolipids have been implicated in anoxia injury, but the pathomechanism is unknown. Here we show that anoxia-associated injury causes accumulation of the non-canonical sphingolipid 1-deoxydihydroceramide (DoxDHCer). Anoxia causes an imbalance between serine and alanine resulting in a switch from normal serine-derived sphinganine biosynthesis to non-canonical alanine-derived 1-deoxysphinganine. 1-Deoxysphinganine is incorporated into DoxDHCer, which impairs actin folding via the cytosolic chaperonin TRiC, leading to growth arrest in yeast, increased cell death upon anoxia-reoxygenation in worms and ischaemia-reperfusion injury in mouse hearts. Prevention of DoxDHCer accumulation in worms and in mouse hearts resulted in decreased anoxia-induced injury. These findings unravel key metabolic changes during oxygen deprivation and point to novel strategies to avoid tissue damage and death.
Mots-clé
Alanine/metabolism, Animals, Animals, Genetically Modified, Caenorhabditis elegans, Cell Division, Chaperonins/genetics, Chaperonins/metabolism, Feeding Behavior, Hypoxia/chemically induced, Ion Channels/metabolism, Mice, Mice, Inbred C57BL, Mutation, Myocardial Reperfusion Injury/prevention & control, Protein Folding/drug effects, Saccharomyces cerevisiae/metabolism, Serine/metabolism, Sphingosine/analogs & derivatives, Sphingosine/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/12/2020 16:33
Dernière modification de la notice
30/01/2021 7:26
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