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Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
- Source :
- Cell. 159(7):1563-1577
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- SummaryThe mechanism by which cells undergo death determines whether dying cells trigger inflammatory responses or remain immunologically silent. Mitochondria play a central role in the induction of cell death, as well as in immune signaling pathways. Here, we identify a mechanism by which mitochondria and downstream proapoptotic caspases regulate the activation of antiviral immunity. In the absence of active caspases, mitochondrial outer membrane permeabilization by Bax and Bak results in the expression of type I interferons (IFNs). This induction is mediated by mitochondrial DNA-dependent activation of the cGAS/STING pathway and results in the establishment of a potent state of viral resistance. Our results show that mitochondria have the capacity to simultaneously expose a cell-intrinsic inducer of the IFN response and to inactivate this response in a caspase-dependent manner. This mechanism provides a dual control, which determines whether mitochondria initiate an immunologically silent or a proinflammatory type of cell death.
- Subjects :
- Male
Programmed cell death
Apoptosis
Mitochondrion
Article
General Biochemistry, Genetics and Molecular Biology
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Caspase
030304 developmental biology
0303 health sciences
biology
Biochemistry, Genetics and Molecular Biology(all)
Intrinsic apoptosis
3. Good health
Cell biology
Caspases
030220 oncology & carcinogenesis
Interferon Type I
biology.protein
Female
Signal transduction
Interferon type I
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 159
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....2261fdd68ac1960aae232631cbe06bac
- Full Text :
- https://doi.org/10.1016/j.cell.2014.11.037