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. and Vince, James E. (2014) Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO reports, 15 9: 982-990. doi:10.15252/embr.201438463


Author 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.
Title Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming
Journal name EMBO reports   Check publisher's open access policy
ISSN 1469-3178
1469-221X
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.15252/embr.201438463
Volume 15
Issue 9
Start page 982
End page 990
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell
Collection year 2015
Language eng
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.
Keyword Apoptosis
Caspase-8
Inflammasome
Mitochondria
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 2 July 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 49 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 52 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 04 Jul 2014, 19:50:45 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences