Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming.

Détails

ID Serval
serval:BIB_B371BC9C013D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming.
Périodique
EMBO Reports
Auteur⸱e⸱s
Allam R., Lawlor K.E., Yu E.C., Mildenhall A.L., Moujalled D.M., Lewis R.S., Ke F., Mason K.D., White M.J., Stacey K.J., Strasser A., O'Reilly L.A., Alexander W., Kile B.T., Vaux D.L., Vince J.E.
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Statut éditorial
Publié
Date de publication
2014
Volume
15
Numéro
9
Pages
982-990
Langue
anglais
Résumé
A current paradigm proposes that mitochondrial damage is a critical determinant of NLRP3 inflammasome activation. Here, we genetically assess whether mitochondrial signalling represents a unified mechanism to explain how NLRP3 is activated by divergent stimuli. Neither co-deletion of the essential executioners of mitochondrial apoptosis BAK and BAX, nor removal of the mitochondrial permeability transition pore component cyclophilin D, nor loss of the mitophagy regulator Parkin, nor deficiency in MAVS affects NLRP3 inflammasome function. In contrast, caspase-8, a caspase essential for death-receptor-mediated apoptosis, is required for efficient Toll-like-receptor-induced inflammasome priming and cytokine production. Collectively, these results demonstrate that mitochondrial apoptosis is not required for NLRP3 activation, and highlight an important non-apoptotic role for caspase-8 in regulating inflammasome activation and pro-inflammatory cytokine levels.
Mots-clé
apoptosis, caspase-8, inflammasome, mitochondria, NLRP3
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/10/2014 9:10
Dernière modification de la notice
20/08/2019 16:22
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