{"data":{"id":"10.6084/m9.figshare.1460843.v6","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1460843.v6","prefix":"10.6084","suffix":"m9.figshare.1460843.v6","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Rohit A Sinha","affiliation":[],"nameIdentifiers":[]},{"name":"Brijesh K Singh","affiliation":[],"nameIdentifiers":[]},{"name":"Zhou, Jin","nameType":"Personal","givenName":"Jin","familyName":"Zhou","affiliation":[],"nameIdentifiers":[]},{"name":"Yajun Wu","affiliation":[],"nameIdentifiers":[]},{"name":"Farah, Benjamin L","nameType":"Personal","givenName":"Benjamin L","familyName":"Farah","affiliation":[],"nameIdentifiers":[]},{"name":"Ohba, Kenji","nameType":"Personal","givenName":"Kenji","familyName":"Ohba","affiliation":[],"nameIdentifiers":[]},{"name":"Lesmana, Ronny","nameType":"Personal","givenName":"Ronny","familyName":"Lesmana","affiliation":[],"nameIdentifiers":[]},{"name":"Gooding, Jessica","nameType":"Personal","givenName":"Jessica","familyName":"Gooding","affiliation":[],"nameIdentifiers":[]},{"name":"Boon-Huat Bay","affiliation":[],"nameIdentifiers":[]},{"name":"Yen, Paul M","nameType":"Personal","givenName":"Paul M","familyName":"Yen","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Genetics"},{"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":"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":"Inorganic Chemistry"},{"subject":"FOS: Chemical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Chemical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Biological Sciences"},{"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":"Chemistry"},{"subject":"Earth and Environmental Sciences"},{"subject":"Evolutionary Biology"},{"subject":"Physiology"},{"subject":"Molecular Biology"},{"subject":"Cell Biology"},{"subject":"Microbiology"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-10-08","dateType":"Created"},{"date":"2016-01-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15548627.2015.1061849","relatedIdentifierType":"DOI"},{"relationType":"IsPreviousVersionOf","relatedIdentifier":"10.6084/m9.figshare.1460843","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["26146832 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":"Currently, there is limited understanding about hormonal regulation of mitochondrial turnover. Thyroid hormone (T\u003csub\u003e3\u003c/sub\u003e) increases oxidative phosphorylation (OXPHOS), which generates reactive oxygen species (ROS) that damage mitochondria. However, the mechanism for maintenance of mitochondrial activity and quality control by this hormone is not known. Here, we used both in vitro and in vivo hepatic cell models to demonstrate that induction of mitophagy by T\u003csub\u003e3\u003c/sub\u003e is coupled to oxidative phosphorylation and ROS production. We show that T\u003csub\u003e3\u003c/sub\u003e induction of ROS activates CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, β) mediated phosphorylation of PRKAA1/AMPK (5′ AMP-activated protein kinase), which in turn phosphorylates ULK1 (unc-51 like autophagy activating kinase 1) leading to its mitochondrial recruitment and initiation of mitophagy. Furthermore, loss of ULK1 in T\u003csub\u003e3\u003c/sub\u003e-treated cells impairs both mitophagy as well as OXPHOS without affecting T\u003csub\u003e3\u003c/sub\u003e induced general autophagy/lipophagy. These findings demonstrate a novel ROS-AMPK-ULK1 mechanism that couples T\u003csub\u003e3\u003c/sub\u003e-induced mitochondrial turnover with activity, wherein mitophagy is necessary not only for removing damaged mitochondria but also for sustaining efficient OXPHOS.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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