Mitofusin-2 boosts innate immunity through the maintenance of aerobic glycolysis and activation of xenophagy in mice
| Autor: | Yi Sak Kim, Jin Kyung Kim, Sang Hee Lee, Eun-Kyeong Jo, Sang Min Jeon, Young Jae Kim, Jihye Kim, Won Do Heo, Jun Young Heo, Min Joung Lee, Yeji Seo, Dong-Wook Hyun, Hyun Sik Kim, Jin-Woo Bae, Soo Yeon Kim, Yang Hoon Huh, Mi-Ja Jung, June-Young Lee, Jin-Man Kim, Jeong Eun Han, Jake Whang, Prashanta Silwal |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 MFN2 Medicine (miscellaneous) Biology General Biochemistry Genetics and Molecular Biology Article GTP Phosphohydrolases 03 medical and health sciences Mice 0302 clinical medicine Mitophagy Macroautophagy Xenophagy Animals Mitochondrial respiratory chain complex I Biology (General) chemistry.chemical_classification Mice Knockout Reactive oxygen species Innate immune system Bacteria Macrophages Bacterial Infections Immunity Innate Cell biology Mitochondria Mice Inbred C57BL 030104 developmental biology chemistry mitochondrial fusion Anaerobic glycolysis Bacterial infection General Agricultural and Biological Sciences Reactive Oxygen Species Infection Glycolysis 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-17 (2021) Communications Biology |
| ISSN: | 2399-3642 |
| Popis: | Mitochondrial 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)-1α 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-1α, 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-1α. 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-1α 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-1α in macrophages during bacterial infection. This study provides insights into how mitochondria-shaping protein is involved in host defense against intracellular bacterial infection. |
| Databáze: | OpenAIRE |
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