RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity

Abstract Mitochondria act as a platform for antiviral innate immunity, and the immune system depends on activation of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) signaling pathway via an adaptor molecule, mitochondrial antiviral signaling. We report that RLR-mediated antiviral in...

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Autores principales:	Takuma Yoshizumi, Hiromi Imamura, Tomohiro Taku, Takahiro Kuroki, Atsushi Kawaguchi, Kaori Ishikawa, Kazuto Nakada, Takumi Koshiba
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe4a330da1d6495e91ed548467d2ed4a
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spelling	oai:doaj.org-article:fe4a330da1d6495e91ed548467d2ed4a2021-12-02T16:06:12ZRLR-mediated antiviral innate immunity requires oxidative phosphorylation activity10.1038/s41598-017-05808-w2045-2322https://doaj.org/article/fe4a330da1d6495e91ed548467d2ed4a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05808-whttps://doaj.org/toc/2045-2322Abstract Mitochondria act as a platform for antiviral innate immunity, and the immune system depends on activation of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) signaling pathway via an adaptor molecule, mitochondrial antiviral signaling. We report that RLR-mediated antiviral innate immunity requires oxidative phosphorylation (OXPHOS) activity, a prominent physiologic function of mitochondria. Cells lacking mitochondrial DNA or mutant cells with respiratory defects exhibited severely impaired virus-induced induction of interferons and proinflammatory cytokines. Recovery of the OXPHOS activity in these mutants, however, re-established RLR-mediated signal transduction. Using in vivo approaches, we found that mice with OXPHOS defects were highly susceptible to viral infection and exhibited significant lung inflammation. Studies to elucidate the molecular mechanism of OXPHOS-coupled immune activity revealed that optic atrophy 1, a mediator of mitochondrial fusion, contributes to regulate the antiviral immune response. Our findings provide evidence for functional coordination between RLR-mediated antiviral innate immunity and the mitochondrial energy-generating system in mammals.Takuma YoshizumiHiromi ImamuraTomohiro TakuTakahiro KurokiAtsushi KawaguchiKaori IshikawaKazuto NakadaTakumi KoshibaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuma Yoshizumi Hiromi Imamura Tomohiro Taku Takahiro Kuroki Atsushi Kawaguchi Kaori Ishikawa Kazuto Nakada Takumi Koshiba RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity
description	Abstract Mitochondria act as a platform for antiviral innate immunity, and the immune system depends on activation of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) signaling pathway via an adaptor molecule, mitochondrial antiviral signaling. We report that RLR-mediated antiviral innate immunity requires oxidative phosphorylation (OXPHOS) activity, a prominent physiologic function of mitochondria. Cells lacking mitochondrial DNA or mutant cells with respiratory defects exhibited severely impaired virus-induced induction of interferons and proinflammatory cytokines. Recovery of the OXPHOS activity in these mutants, however, re-established RLR-mediated signal transduction. Using in vivo approaches, we found that mice with OXPHOS defects were highly susceptible to viral infection and exhibited significant lung inflammation. Studies to elucidate the molecular mechanism of OXPHOS-coupled immune activity revealed that optic atrophy 1, a mediator of mitochondrial fusion, contributes to regulate the antiviral immune response. Our findings provide evidence for functional coordination between RLR-mediated antiviral innate immunity and the mitochondrial energy-generating system in mammals.
format	article
author	Takuma Yoshizumi Hiromi Imamura Tomohiro Taku Takahiro Kuroki Atsushi Kawaguchi Kaori Ishikawa Kazuto Nakada Takumi Koshiba
author_facet	Takuma Yoshizumi Hiromi Imamura Tomohiro Taku Takahiro Kuroki Atsushi Kawaguchi Kaori Ishikawa Kazuto Nakada Takumi Koshiba
author_sort	Takuma Yoshizumi
title	RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity
title_short	RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity
title_full	RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity
title_fullStr	RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity
title_full_unstemmed	RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity
title_sort	rlr-mediated antiviral innate immunity requires oxidative phosphorylation activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fe4a330da1d6495e91ed548467d2ed4a
work_keys_str_mv	AT takumayoshizumi rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT hiromiimamura rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT tomohirotaku rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT takahirokuroki rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT atsushikawaguchi rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT kaoriishikawa rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT kazutonakada rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity AT takumikoshiba rlrmediatedantiviralinnateimmunityrequiresoxidativephosphorylationactivity
_version_	1718385125413093376

RLR-mediated antiviral innate immunity requires oxidative phosphorylation activity

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