{"data":{"id":"10.6084/m9.figshare.1581618","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1581618","prefix":"10.6084","suffix":"m9.figshare.1581618","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Chul-Su Yang","affiliation":[],"nameIdentifiers":[]},{"name":"Jwa-Jin Kim","affiliation":[],"nameIdentifiers":[]},{"name":"Lee, Hye-Mi","nameType":"Personal","givenName":"Hye-Mi","familyName":"Lee","affiliation":[],"nameIdentifiers":[]},{"name":"Jin, Hyo Sun","nameType":"Personal","givenName":"Hyo Sun","familyName":"Jin","affiliation":[],"nameIdentifiers":[]},{"name":"Lee, Sang-Hee","nameType":"Personal","givenName":"Sang-Hee","familyName":"Lee","affiliation":[],"nameIdentifiers":[]},{"name":"Kim, Soung Jung","nameType":"Personal","givenName":"Soung Jung","familyName":"Kim","affiliation":[],"nameIdentifiers":[]},{"name":"Kim, Jin-Man","nameType":"Personal","givenName":"Jin-Man","familyName":"Kim","affiliation":[],"nameIdentifiers":[]},{"name":"Yong-Mahn Han","affiliation":[],"nameIdentifiers":[]},{"name":"Myung-Shik Lee","affiliation":[],"nameIdentifiers":[]},{"name":"Kweon, Gi Ryang","nameType":"Personal","givenName":"Gi Ryang","familyName":"Kweon","affiliation":[],"nameIdentifiers":[]},{"name":"Minho Shong","affiliation":[],"nameIdentifiers":[]},{"name":"Eun-Kyeong Jo","affiliation":[],"nameIdentifiers":[]},{"name":"Park, Ji-Hoon","nameType":"Personal","givenName":"Ji-Hoon","familyName":"Park","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2014,"subjects":[{"subject":"110309 Infectious Diseases","subjectScheme":"FOR"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cancer"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Meta Science"},{"subject":"Chemistry"},{"subject":"Earth and Environmental Sciences"},{"subject":"Physiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Cell Biology"},{"subject":"Microbiology"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-10-21","dateType":"Created"},{"date":"2015-10-21","dateType":"Updated"},{"date":"2014","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.4161/auto.28072","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["5715538 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"AMP-activated protein kinase (AMPK) is a crucial energy sensor and plays a key role in integration of cellular functions to maintain homeostasis. Despite this, it is largely unknown whether targeting the AMPK pathway can be used as a therapeutic strategy for infectious diseases. Herein, we show that AMPK activation robustly induces antibacterial autophagy, which contributes to antimicrobial defense against \u003ci\u003eMycobacterium tuberculosis\u003c/i\u003e (Mtb). AMPK activation led to inhibition of Mtb-induced phosphorylation of the mechanistic target of rapamycin (MTOR) in macrophages. In addition, AMPK activation increased the genes involved in oxidative phosphorylation, mitochondrial ATP production, and biogenesis in Mtb-infected macrophages. Notably, peroxisome proliferator-activated receptor-gamma, coactivator 1α (PPARGC1A) was required for AMPK-mediated antimicrobial activity, as well as enhancement of mitochondrial function and biogenesis, in macrophages. Further, the AMPK-PPARGC1A pathway was involved in the upregulation of multiple autophagy-related genes via CCAAT/enhancer binding protein (C/EBP), β (CEBPB). PPARGC1A knockdown inhibited the AMPK-mediated induction of autophagy and impaired the fusion of phagosomes with MAP1LC3B (LC3B) autophagosomes in Mtb-infected macrophages. The link between autophagy, mitochondrial function, and antimicrobial activity was further demonstrated by studying LysMCre-mediated knockout of \u003ci\u003eatg7\u003c/i\u003e, demonstrating mitochondrial ultrastructural defects and dysfunction, as well as blockade of antimicrobial activity against mycobacteria. Collectively, our results identify the AMPK-PPARGC1A axis as contributing to autophagy activation leading to an antimicrobial response, as a novel host defense mechanism.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjEvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLjE1ODE2MTg8L2lkZW50aWZpZXI+CiAgPGNyZWF0b3JzPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5DaHVsLVN1IFlhbmc8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5Kd2EtSmluIEtpbTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkh5ZS1NaSBMZWU8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5IeW8gU3VuIEppbjwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlNhbmctSGVlIExlZTwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlNvdW5nIEp1bmcgS2ltPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+SmluLU1hbiBLaW08L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5Zb25nLU1haG4gSGFuPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+TXl1bmctU2hpayBMZWU8L2NyZWF0b3JOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5HaSBSeWFuZyBLd2VvbjwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPk1pbmhvIFNob25nPC9jcmVhdG9yTmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+RXVuLUt5ZW9uZyBKbzwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkppLUhvb24gUGFyazwvY3JlYXRvck5hbWU+CiAgICA8L2NyZWF0b3I+CiAgPC9jcmVhdG9ycz4KICA8dGl0bGVzPgogICAgPHRpdGxlPlRoZSBBTVBLLVBQQVJHQzFBIHBhdGh3YXkgaXMgcmVxdWlyZWQgZm9yIGFudGltaWNyb2JpYWwgaG9zdCBkZWZlbnNlIHRocm91Z2ggYWN0aXZhdGlvbiBvZiBhdXRvcGhhZ3k8L3RpdGxlPgogIDwvdGl0bGVzPgogIDxkZXNjcmlwdGlvbnM+CiAgICA8ZGVzY3JpcHRpb24gZGVzY3JpcHRpb25UeXBlPSJBYnN0cmFjdCI+Jmx0O2RpdiZndDsmbHQ7cCZndDtBTVAtYWN0aXZhdGVkIHByb3RlaW4ga2luYXNlIChBTVBLKSBpcyBhIGNydWNpYWwgZW5lcmd5IHNlbnNvciBhbmQgcGxheXMgYSBrZXkgcm9sZSBpbiBpbnRlZ3JhdGlvbiBvZiBjZWxsdWxhciBmdW5jdGlvbnMgdG8gbWFpbnRhaW4gaG9tZW9zdGFzaXMuIERlc3BpdGUgdGhpcywgaXQgaXMgbGFyZ2VseSB1bmtub3duIHdoZXRoZXIgdGFyZ2V0aW5nIHRoZSBBTVBLIHBhdGh3YXkgY2FuIGJlIHVzZWQgYXMgYSB0aGVyYXBldXRpYyBzdHJhdGVneSBmb3IgaW5mZWN0aW91cyBkaXNlYXNlcy4gSGVyZWluLCB3ZSBzaG93IHRoYXQgQU1QSyBhY3RpdmF0aW9uIHJvYnVzdGx5IGluZHVjZXMgYW50aWJhY3RlcmlhbCBhdXRvcGhhZ3ksIHdoaWNoIGNvbnRyaWJ1dGVzIHRvIGFudGltaWNyb2JpYWwgZGVmZW5zZSBhZ2FpbnN0ICZsdDtpJmd0O015Y29iYWN0ZXJpdW0gdHViZXJjdWxvc2lzJmx0Oy9pJmd0OyAoTXRiKS4gQU1QSyBhY3RpdmF0aW9uIGxlZCB0byBpbmhpYml0aW9uIG9mIE10Yi1pbmR1Y2VkIHBob3NwaG9yeWxhdGlvbiBvZiB0aGUgbWVjaGFuaXN0aWMgdGFyZ2V0IG9mIHJhcGFteWNpbiAoTVRPUikgaW4gbWFjcm9waGFnZXMuIEluIGFkZGl0aW9uLCBBTVBLIGFjdGl2YXRpb24gaW5jcmVhc2VkIHRoZSBnZW5lcyBpbnZvbHZlZCBpbiBveGlkYXRpdmUgcGhvc3Bob3J5bGF0aW9uLCBtaXRvY2hvbmRyaWFsIEFUUCBwcm9kdWN0aW9uLCBhbmQgYmlvZ2VuZXNpcyBpbiBNdGItaW5mZWN0ZWQgbWFjcm9waGFnZXMuIE5vdGFibHksIHBlcm94aXNvbWUgcHJvbGlmZXJhdG9yLWFjdGl2YXRlZCByZWNlcHRvci1nYW1tYSwgY29hY3RpdmF0b3IgMc6xIChQUEFSR0MxQSkgd2FzIHJlcXVpcmVkIGZvciBBTVBLLW1lZGlhdGVkIGFudGltaWNyb2JpYWwgYWN0aXZpdHksIGFzIHdlbGwgYXMgZW5oYW5jZW1lbnQgb2YgbWl0b2Nob25kcmlhbCBmdW5jdGlvbiBhbmQgYmlvZ2VuZXNpcywgaW4gbWFjcm9waGFnZXMuIEZ1cnRoZXIsIHRoZSBBTVBLLVBQQVJHQzFBIHBhdGh3YXkgd2FzIGludm9sdmVkIGluIHRoZSB1cHJlZ3VsYXRpb24gb2YgbXVsdGlwbGUgYXV0b3BoYWd5LXJlbGF0ZWQgZ2VuZXMgdmlhIENDQUFUL2VuaGFuY2VyIGJpbmRpbmcgcHJvdGVpbiAoQy9FQlApLCDOsiAoQ0VCUEIpLiBQUEFSR0MxQSBrbm9ja2Rvd24gaW5oaWJpdGVkIHRoZSBBTVBLLW1lZGlhdGVkIGluZHVjdGlvbiBvZiBhdXRvcGhhZ3kgYW5kIGltcGFpcmVkIHRoZSBmdXNpb24gb2YgcGhhZ29zb21lcyB3aXRoIE1BUDFMQzNCIChMQzNCKSBhdXRvcGhhZ29zb21lcyBpbiBNdGItaW5mZWN0ZWQgbWFjcm9waGFnZXMuIFRoZSBsaW5rIGJldHdlZW4gYXV0b3BoYWd5LCBtaXRvY2hvbmRyaWFsIGZ1bmN0aW9uLCBhbmQgYW50aW1pY3JvYmlhbCBhY3Rpdml0eSB3YXMgZnVydGhlciBkZW1vbnN0cmF0ZWQgYnkgc3R1ZHlpbmcgTHlzTUNyZS1tZWRpYXRlZCBrbm9ja291dCBvZiAmbHQ7aSZndDthdGc3Jmx0Oy9pJmd0OywgZGVtb25zdHJhdGluZyBtaXRvY2hvbmRyaWFsIHVsdHJhc3RydWN0dXJhbCBkZWZlY3RzIGFuZCBkeXNmdW5jdGlvbiwgYXMgd2VsbCBhcyBibG9ja2FkZSBvZiBhbnRpbWljcm9iaWFsIGFjdGl2aXR5IGFnYWluc3QgbXljb2JhY3RlcmlhLiBDb2xsZWN0aXZlbHksIG91ciByZXN1bHRzIGlkZW50aWZ5IHRoZSBBTVBLLVBQQVJHQzFBIGF4aXMgYXMgY29udHJpYnV0aW5nIHRvIGF1dG9waGFneSBhY3RpdmF0aW9uIGxlYWRpbmcgdG8gYW4gYW50aW1pY3JvYmlhbCByZXNwb25zZSwgYXMgYSBub3ZlbCBob3N0IGRlZmVuc2UgbWVjaGFuaXNtLiZsdDsvcCZndDsmbHQ7L2RpdiZndDs8L2Rlc2NyaXB0aW9uPgogIDwvZGVzY3JpcHRpb25zPgogIDxzdWJqZWN0cz4KICAgIDxzdWJqZWN0IHNjaGVtZVVSST0iaHR0cDovL3d3dy5hYnMuZ292LmF1L2F1c3N0YXRzL2Fic0AubnNmLzAvNkJCNDI3QUI5Njk2QzIyNUNBMjU3NDE4MDAwNDQ2M0UiIHN1YmplY3RTY2hlbWU9IkZPUiI+MTEwMzA5IEluZmVjdGlvdXMgRGlzZWFzZXM8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5DYW5jZXI8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5JbW11bm9sb2d5PC9zdWJqZWN0PgogICAgPHN1YmplY3Q+TWV0YSBTY2llbmNlPC9zdWJqZWN0PgogICAgPHN1Y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