Papers

Peer-reviewed
Jun, 2013

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

Genes to Cells
  • Tomohiko Okazaki
  • ,
  • Maiko Higuchi
  • ,
  • Yukiko Gotoh

Volume
18
Number
6
First page
493
Last page
501
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1111/gtc.12052

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. © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Link information
DOI
https://doi.org/10.1111/gtc.12052
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23574001
ID information
  • DOI : 10.1111/gtc.12052
  • ISSN : 1356-9597
  • ISSN : 1365-2443
  • Pubmed ID : 23574001
  • SCOPUS ID : 84878351597

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