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Mitochondrial localization of the antiviral signaling adaptor IPS-1 is important for its induction of caspase activation.

Authors
  • Okazaki, Tomohiko
  • Higuchi, Maiko
  • Gotoh, Yukiko
Type
Published Article
Journal
Genes to Cells
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2013
Volume
18
Issue
6
Pages
493–501
Identifiers
DOI: 10.1111/gtc.12052
PMID: 23574001
Source
Medline
License
Unknown

Abstract

The RIG-I-like receptor (RLR) family of intracellular receptors detects viral nucleic acids and transmits an antiviral signal through the adaptor IPS-1. IPS-1 activation triggers host defense mechanisms, including rapid production of type I interferon (IFN), such as IFN-β, and induction of apoptosis. IPS-1 is mainly localized to mitochondria, and this localization has been proposed to be essential for inducing production of type I IFN and IFN-stimulated genes (ISGs). However, the importance of this mitochondrial localization of IPS-1 in executing apoptosis has remained unclear. Here, using IPS-1 mutants that were directed to specific subcellular locations such as cytoplasm, plasma membrane and mitochondria, we found that IPS-1's localization to mitochondria is important to activate caspase, but not to signal for IFN-β gene induction. We also found that IPS-1 possesses a BH3-like motif, which is commonly found among members of the Bcl-2 family. Mutations within this motif promoted IPS-1-induced caspase activation, suggesting that this domain acts as an intrinsic inhibitor domain of apoptosis induction. These results establish that the mitochondrial location of IPS-1 is essential to its ability to induce apoptosis.

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