title: Mitochondrial localization of the antiviral signaling adaptor IPS-1 is important for its induction of caspase activation.
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.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okazaki
authors.forename: Maiko
authors.initials: M
authors.lastname: Higuchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D020169:Caspases