Mitofusin-2 boosts innate immunity through the maintenance of aerobic glycolysis and activation of xenophagy in mice

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dc.contributor.authorSilwal, Prashantako
dc.contributor.authorKim, Jin Kyungko
dc.contributor.authorJeon, Sang Minko
dc.contributor.authorLee, June-Youngko
dc.contributor.authorKim, Young Jaeko
dc.contributor.authorKim, Yi Sakko
dc.contributor.authorSeo, Yejiko
dc.contributor.authorKim, Jihyeko
dc.contributor.authorKim, Soo Yeonko
dc.contributor.authorLee, Min Joungko
dc.contributor.authorHeo, Jun Youngko
dc.contributor.authorJung, Mi-Jako
dc.contributor.authorKim, Hyun Sikko
dc.contributor.authorHyun, Dong-Wookko
dc.contributor.authorHan, Jeong Eunko
dc.contributor.authorWhang, Jakeko
dc.contributor.authorHuh, Yang Hoonko
dc.contributor.authorLee, Sang-Heeko
dc.contributor.authorHeo, Won Doko
dc.contributor.authorKim, Jin-Manko
dc.contributor.authorBae, Jin-Wooko
dc.contributor.authorJo, Eun-Kyeongko
dc.date.accessioned2021-06-08T02:30:17Z-
dc.date.available2021-06-08T02:30:17Z-
dc.date.created2021-06-07-
dc.date.created2021-06-07-
dc.date.created2021-06-07-
dc.date.issued2021-05-
dc.identifier.citationCOMMUNICATIONS BIOLOGY, v.4, no.1-
dc.identifier.issn2399-3642-
dc.identifier.urihttp://hdl.handle.net/10203/285595-
dc.description.abstractMitochondrial function and innate immunity are intimately linked; however, the mechanisms how mitochondrion-shaping proteins regulate innate host defense remains largely unknown. Herein we show that mitofusin-2 (MFN2), a mitochondrial fusion protein, promotes innate host defense through the maintenance of aerobic glycolysis and xenophagy via hypoxia-inducible factor (HIF)-1 alpha during intracellular bacterial infection. Myeloid-specific MFN2 deficiency in mice impaired the antimicrobial and inflammatory responses against mycobacterial and listerial infection. Mechanistically, MFN2 was required for the enhancement of inflammatory signaling through optimal induction of aerobic glycolysis via HIF-1 alpha, which is activated by mitochondrial respiratory chain complex I and reactive oxygen species, in macrophages. MFN2 did not impact mitophagy during infection; however, it promoted xenophagy activation through HIF-1 alpha. In addition, MFN2 interacted with the late endosomal protein Rab7, to facilitate xenophagy during mycobacterial infection. Our findings reveal the mechanistic regulations by which MFN2 tailors the innate host defense through coordinated control of immunometabolism and xenophagy via HIF-1 alpha during bacterial infection. Silwal, Kim et al. show that mitofusin-2 (MFN2), a mitochondrial fusion protein, promotes innate host defense through coordinated orchestration of immunometabolism and xenophagy via HIF-1 alpha in macrophages during bacterial infection. This study provides insights into how mitochondria-shaping protein is involved in host defense against intracellular bacterial infection.-
dc.languageEnglish-
dc.publisherNATURE RESEARCH-
dc.titleMitofusin-2 boosts innate immunity through the maintenance of aerobic glycolysis and activation of xenophagy in mice-
dc.typeArticle-
dc.identifier.wosid000656215900001-
dc.identifier.scopusid2-s2.0-85105563456-
dc.type.rimsART-
dc.citation.volume4-
dc.citation.issue1-
dc.citation.publicationnameCOMMUNICATIONS BIOLOGY-
dc.identifier.doi10.1038/s42003-021-02073-6-
dc.contributor.localauthorHeo, Won Do-
dc.contributor.nonIdAuthorSilwal, Prashanta-
dc.contributor.nonIdAuthorKim, Jin Kyung-
dc.contributor.nonIdAuthorJeon, Sang Min-
dc.contributor.nonIdAuthorLee, June-Young-
dc.contributor.nonIdAuthorKim, Young Jae-
dc.contributor.nonIdAuthorKim, Yi Sak-
dc.contributor.nonIdAuthorKim, Jihye-
dc.contributor.nonIdAuthorKim, Soo Yeon-
dc.contributor.nonIdAuthorLee, Min Joung-
dc.contributor.nonIdAuthorHeo, Jun Young-
dc.contributor.nonIdAuthorJung, Mi-Ja-
dc.contributor.nonIdAuthorKim, Hyun Sik-
dc.contributor.nonIdAuthorHyun, Dong-Wook-
dc.contributor.nonIdAuthorHan, Jeong Eun-
dc.contributor.nonIdAuthorWhang, Jake-
dc.contributor.nonIdAuthorHuh, Yang Hoon-
dc.contributor.nonIdAuthorLee, Sang-Hee-
dc.contributor.nonIdAuthorKim, Jin-Man-
dc.contributor.nonIdAuthorBae, Jin-Woo-
dc.contributor.nonIdAuthorJo, Eun-Kyeong-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusMITOCHONDRIAL DYNAMICS-
dc.subject.keywordPlusENDOPLASMIC-RETICULUM-
dc.subject.keywordPlusFUSION-
dc.subject.keywordPlusCELL-
dc.subject.keywordPlusAUTOPHAGY-
dc.subject.keywordPlusFISSION-
dc.subject.keywordPlusIMMUNOMETABOLISM-
dc.subject.keywordPlusMACROPHAGES-
dc.subject.keywordPlusMATURATION-
dc.subject.keywordPlusSTRESS-
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