AMPK Promotes Xenophagy through Priming of Autophagic Kinases upon Detection of Bacterial Outer Membrane Vesicles
| Autor: | Nicholas D. LeBlond, Reham M. Alsaadi, Ryan Reshke, Truc T. Losier, Morgan D. Fullerton, Derrick Gibbings, Ryan C. Russell, Mercy Akuma, Zhihao Guo, Yujin Suk, Subash Sad, François-Xavier Campbell-Valois, Olivia C. McKee-Muir |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Bacterial outer membrane vesicles mTORC1 Mechanistic Target of Rapamycin Complex 1 General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine AMP-Activated Protein Kinase Kinases Mice Inbred NOD Salmonella Macroautophagy Xenophagy Animals Autophagy-Related Protein-1 Homolog Humans lcsh:QH301-705.5 PI3K/AKT/mTOR pathway Cells Cultured Chemistry Macrophages Autophagy AMPK ULK1 HCT116 Cells Class III Phosphatidylinositol 3-Kinases Autophagic Punctum Cell biology 030104 developmental biology Bacterial Outer Membrane HEK293 Cells lcsh:Biology (General) Host-Pathogen Interactions MCF-7 Cells Bacterial outer membrane Protein Kinases 030217 neurology & neurosurgery |
| Zdroj: | Autophagy Cell Reports, Vol 26, Iss 8, Pp 2150-2165.e5 (2019) |
| ISSN: | 2211-1247 |
| Popis: | Summary: The autophagy pathway is an essential facet of the innate immune response, capable of rapidly targeting intracellular bacteria. However, the initial signaling regulating autophagy induction in response to pathogens remains largely unclear. Here, we report that AMPK, an upstream activator of the autophagy pathway, is stimulated upon detection of pathogenic bacteria, before bacterial invasion. Bacterial recognition occurs through the detection of outer membrane vesicles. We found that AMPK signaling relieves mTORC1-mediated repression of the autophagy pathway in response to infection, positioning the cell for a rapid induction of autophagy. Moreover, activation of AMPK and inhibition of mTORC1 in response to bacteria is not accompanied by an induction of bulk autophagy. However, AMPK signaling is required for the selective targeting of bacteria-containing vesicles by the autophagy pathway through the activation of pro-autophagic kinase complexes. These results demonstrate a key role for AMPK signaling in coordinating the rapid autophagic response to bacteria. : Autophagy is a degradative process that host cells use to cope with invading pathogens, but its earliest activation is unclear. Losier et al. describe a signaling pathway that is activated by the detection of extracellular bacteria-derived OMVs. This autophagy-initiating pathway results in selective targeting and degradation of bacteria rather than cytoplasmic components. Keywords: autophagy, AMPK, mTOR, ULK1, VPS34, xenophagy, OMV, Salmonella, outer membrane vesicles |
| Databáze: | OpenAIRE |
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