| First Author | Vince JE | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 9 | Pages | 2339-2353.e4 |
| PubMed ID | 30485804 | Mgi Jnum | J:270778 |
| Mgi Id | MGI:6278712 | Doi | 10.1016/j.celrep.2018.10.103 |
| Citation | Vince JE, et al. (2018) The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1beta Activation. Cell Rep 25(9):2339-2353.e4 |
| abstractText | 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-1beta. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1beta 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-1beta maturation and secretion. Conversely, the pyroptotic cell death effectors gasdermin D and gasdermin E are not essential for BAX/BAK-induced IL-1beta 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-1beta activation is often associated with cellular stress, such as during chemotherapy. |
