Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA.
Cell
; 159(7): 1563-77, 2014 Dec 18.
Article
in En
| MEDLINE
| ID: mdl-25525875
ABSTRACT
The 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Interferon Type I
/
Apoptosis
/
Caspases
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2014
Document type:
Article
Affiliation country:
United States