Caspase-1 cleaves Bid to release mitochondrial SMAC and drive secondary necrosis in the absence of GSDMD.

Details

Serval ID
serval:BIB_0F375D8FC416
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Caspase-1 cleaves Bid to release mitochondrial SMAC and drive secondary necrosis in the absence of GSDMD.
Journal
Life science alliance
Author(s)
Heilig R., Dilucca M., Boucher D., Chen K.W., Hancz D., Demarco B., Shkarina K., Broz P.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Publication state
Published
Issued date
06/2020
Peer-reviewed
Oui
Volume
3
Number
6
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Caspase-1 drives a lytic inflammatory cell death named pyroptosis by cleaving the pore-forming cell death executor gasdermin-D (GSDMD). Gsdmd deficiency, however, only delays cell lysis, indicating that caspase-1 controls alternative cell death pathways. Here, we show that in the absence of GSDMD, caspase-1 activates apoptotic initiator and executioner caspases and triggers a rapid progression into secondary necrosis. GSDMD-independent cell death required direct caspase-1-driven truncation of Bid and generation of caspase-3 p19/p12 by either caspase-8 or caspase-9. tBid-induced mitochondrial outer membrane permeabilization was also required to drive SMAC release and relieve inhibitor of apoptosis protein inhibition of caspase-3, thereby allowing caspase-3 auto-processing to the fully active p17/p12 form. Our data reveal that cell lysis in inflammasome-activated Gsdmd-deficient cells is caused by a synergistic effect of rapid caspase-1-driven activation of initiator caspases-8/-9 and Bid cleavage, resulting in an unusually fast activation of caspase-3 and immediate transition into secondary necrosis. This pathway might be advantageous for the host in counteracting pathogen-induced inhibition of GSDMD but also has implications for the use of GSDMD inhibitors in immune therapies for caspase-1-dependent inflammatory disease.
Pubmed
Open Access
Yes
Create date
02/05/2020 15:05
Last modification date
20/05/2020 6:26
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