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Cited by 235

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The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation

Open access
Vince, James E., De Nardo, Dominic, Gao, Wenqing, Vince, Angelina J., Hall, Cathrine, McArthur, Kate, Simpson, Daniel, Vijayaraj, Swarna, Lindqvist, Lisa M., Bouillet, Philippe, Rizzacasa, Mark A., Man, Si Ming, Silke, John, Masters, Seth L., Lessene, Guillaume, Huang, David C.S., Gray, Daniel H.D., Kile, Benjamin T., Shao, Feng, Lawlor, Kate E.·2018·Cell Reports

Abstract

Intrinsic apoptosis resulting from BAX/BAK-mediated mitochondrial membrane damage is regarded as immunologically silent. We show here that in macrophages, BAX/BAK activation results in inhibitor of apoptosis (IAP) protein degradation to promote caspase-8-mediated activation of IL-1β. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1β maturation that requires potassium efflux. Remarkably, following BAX/BAK activation, the apoptotic executioner caspases, caspase-3 and -7, act upstream of both caspase-8 and NLRP3-induced IL-1β maturation and secretion. Conversely, the pyroptotic cell death effectors gasdermin D and gasdermin E are not essential for BAX/BAK-induced IL-1β release. These findings highlight that innate immune cells undergoing BAX/BAK-mediated apoptosis have the capacity to generate pro-inflammatory signals and provide an explanation as to why IL-1β activation is often associated with cellular stress, such as during chemotherapy.

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Metadata

Authors
Vince, J. E., De Nardo, D., Gao, W., Vince, A. J., Hall, C., McArthur, K., Simpson, D., Vijayaraj, S., Lindqvist, L. M., Bouillet, P., Rizzacasa, M. A., Man, S. M., Silke, J., Masters, S. L., Lessene, G., Huang, D. C. S., Gray, D. H. D., Kile, B. T., Shao, F., & Lawlor, K. E.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2018-11
Volume
25
Issue
9
Pages
2339-2353.e4
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2902287405
Cited by
235
References
22
FWCI
7.46
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation. https://app.cochat.ai/papers/10.1016/j.celrep.2018.10.103
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Vince, J. E., De Nardo, D., Gao, W., Vince, A. J., Hall, C., McArthur, K., Simpson, D., Vijayaraj, S., Lindqvist, L. M., Bouillet, P., Rizzacasa, M. A., Man, S. M., Silke, J., Masters, S. L., Lessene, G., Huang, D. C. S., Gray, D. H. D., Kile, B. T., Shao, F., & Lawlor, K. E. (2018). The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation. Cell Reports. https://doi.org/10.1016/j.celrep.2018.10.103

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.