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Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming.
Allam, Ramanjaneyulu; Lawlor, Kate E; Yu, Eric Chi-Wang; Mildenhall, Alison L; Moujalled, Donia M; Lewis, Rowena S; Ke, Francine; Mason, Kylie D; White, Michael J; Stacey, Katryn J; Strasser, Andreas; O'Reilly, Lorraine A; Alexander, Warren; Kile, Benjamin T; Vaux, David L; Vince, James E.
Afiliación
  • Allam R; Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
  • Lawlor KE; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Yu EC; Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
  • Mildenhall AL; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Moujalled DM; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Lewis RS; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Ke F; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Mason KD; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • White MJ; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Stacey KJ; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld, Australia.
  • Strasser A; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • O'Reilly LA; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Alexander W; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Kile BT; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Vaux DL; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
  • Vince JE; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia vince@wehi.edu.au.
EMBO Rep ; 15(9): 982-90, 2014 Sep.
Article en En | MEDLINE | ID: mdl-24990442
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Portadoras / Caspasa 8 / Inflamasomas / Mitocondrias Límite: Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article País de afiliación: Suiza
Texto completo
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Proteínas Portadoras / Caspasa 8 / Inflamasomas / Mitocondrias Límite: Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article País de afiliación: Suiza