Mitochondrial apoptosis is dispensable for NLRP 3 inflammasome activation but non‐apoptotic caspase‐8 is required for inflammasome priming
| Autor: | Kylie D. Mason, Ramanjaneyulu Allam, Warren S. Alexander, Alison L Mildenhall, Eric Chi-Wang Yu, Benjamin T. Kile, Francine Ke, Donia M Moujalled, Lorraine A. O'Reilly, Rowena S. Lewis, Michael J. White, Andreas Strasser, Kate E. Lawlor, Katryn J. Stacey, David L. Vaux, James E Vince |
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| Rok vydání: | 2014 |
| Předmět: |
Programmed cell death
Inflammasomes Ubiquitin-Protein Ligases Interleukin-1beta Mitochondrial Degradation Apoptosis Bone Marrow Cells Biology Mitochondrion Caspase 8 Biochemistry Cyclophilins AIM2 NLR Family Pyrin Domain-Containing 3 Protein Mitophagy Autophagy Genetics medicine Humans Molecular Biology Cells Cultured integumentary system Toll-Like Receptors Scientific Reports Inflammasome Mitochondria Cell biology Mitochondrial permeability transition pore Carrier Proteins Cyclophilin D medicine.drug |
| Zdroj: | EMBO reports. 15:982-990 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201438463 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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