Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy

dc.contributor.authorDrake, Joshua C.en
dc.contributor.authorWilson, Rebecca J.en
dc.contributor.authorLaker, Rhianna C.en
dc.contributor.authorGuan, Yuntianen
dc.contributor.authorSpaulding, Hannah R.en
dc.contributor.authorNichenko, Anna S.en
dc.contributor.authorShen, Wenqingen
dc.contributor.authorShang, Huayuen
dc.contributor.authorDorn, Mayaen
dc.contributor.authorHuang, Kianen
dc.contributor.authorZhang, Meien
dc.contributor.authorBandara, Aloka B.en
dc.contributor.authorBrisendine, Matthew H.en
dc.contributor.authorKashatus, Jennifer A.en
dc.contributor.authorSharma, Poonam R.en
dc.contributor.authorYoung, Alexanderen
dc.contributor.authorGautam, Jitendraen
dc.contributor.authorCao, Ruofanen
dc.contributor.authorWallrabe, Horsten
dc.contributor.authorChang, Paul A.en
dc.contributor.authorWong, Michaelen
dc.contributor.authorDesjardins, Eric M.en
dc.contributor.authorHawley, Simon A.en
dc.contributor.authorChrist, George J.en
dc.contributor.authorKashatus, David F.en
dc.contributor.authorMiller, Clint L.en
dc.contributor.authorWolf, Matthew J.en
dc.contributor.authorPeriasamy, Ammasien
dc.contributor.authorSteinberg, Gregory R.en
dc.contributor.authorHardie, D. Grahameen
dc.contributor.authorYan, Zhenen
dc.date.accessioned2022-01-07T15:47:50Zen
dc.date.available2022-01-07T15:47:50Zen
dc.date.issued2021-09-14en
dc.date.updated2022-01-07T15:47:47Zen
dc.description.abstractMitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5′ AMP-activated protein kinase (AMPKα1/ α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment.en
dc.description.versionPublished versionen
dc.format.extent10 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e2025932118 (Article number)en
dc.identifier.doihttps://doi.org/10.1073/pnas.2025932118en
dc.identifier.eissn1091-6490en
dc.identifier.issn0027-8424en
dc.identifier.issue37en
dc.identifier.orcidBandara, Aloka [0000-0002-2562-1810]en
dc.identifier.orcidDrake, Joshua [0000-0001-6658-4975]en
dc.identifier.other2025932118 (PII)en
dc.identifier.pmid34493662en
dc.identifier.urihttp://hdl.handle.net/10919/107452en
dc.identifier.volume118en
dc.language.isoenen
dc.publisherNational Academy of Sciencesen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000703999300020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmitochondriaen
dc.subjectAMPKen
dc.subjectskeletal muscleen
dc.subjectexerciseen
dc.subjectmitophagyen
dc.subjectACTIVATED PROTEIN-KINASEen
dc.subjectSKELETAL-MUSCLEen
dc.subjectSUBCELLULAR-DISTRIBUTIONen
dc.subjectRAT-LIVERen
dc.subjectMITOTIMERen
dc.subjectRETICULUMen
dc.subjectAUTOPHAGYen
dc.subjectGENEen
dc.subjectSITEen
dc.subjectPHOSPHORYLATIONen
dc.subjectAMPKen
dc.subject.meshAMP-Activated Protein Kinasesen
dc.subject.meshAnimalsen
dc.subject.meshEnergy Metabolismen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiceen
dc.subject.meshMitochondriaen
dc.subject.meshMitophagyen
dc.subject.meshPhysical Conditioning, Animalen
dc.titleMitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagyen
dc.title.serialProceedings of the National Academy of Sciences of the United States of Americaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-08-05en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exerciseen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exercise/D. Brown Groupen
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