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Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA.

Authors :
Rongvaux A
Jackson R
Harman CC
Li T
West AP
de Zoete MR
Wu Y
Yordy B
Lakhani SA
Kuan CY
Taniguchi T
Shadel GS
Chen ZJ
Iwasaki A
Flavell RA
Source :
Cell [Cell] 2014 Dec 18; Vol. 159 (7), pp. 1563-77.
Publication Year :
2014

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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4172
Volume :
159
Issue :
7
Database :
MEDLINE
Journal :
Cell
Publication Type :
Academic Journal
Accession number :
25525875
Full Text :
https://doi.org/10.1016/j.cell.2014.11.037