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Mimicking mitochondrial dysfunction using respiratory chain\/oxidative phosphorylation inhibitors resulted in enhanced expression and release of FGF21 by muscle cells. The increased production of reactive oxygen species, subsequent induction of p38 MAPK (mitogen-activated protein kinase) and activation of an ATF2 (activating transcription factor 2)-binding site at the proximal promoter region of the FGF21 gene was found to be a major mechanism linking mitochondrial dysfunction with enhanced FGF21 gene transcription in myogenic cells. The myogenic factor MyoD was required for the induction of FGF21 gene transcription by mitochondrial dysfunction, thus explaining the preferential response of muscle cells to mitochondrial dysfunction-induced FGF21 expression and secretion. FGF21 release by muscle cells in response to mitochondrial alterations may represent a physiological mechanism by which the sensing of internal energetic status by muscles results in the release of FGF21 to favour systemic metabolic adaptations.<\/jats:p>","DOI":"10.1042\/bj20140403","type":"journal-article","created":{"date-parts":[[2014,7,24]],"date-time":"2014-07-24T08:51:38Z","timestamp":1406191898000},"page":"191-199","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["FGF21 expression and release in muscle cells: involvement of MyoD and regulation by mitochondria-driven signalling"],"prefix":"10.1042","volume":"463","author":[{"given":"Francesc","family":"Ribas","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, and Institute of Biomedicine (IBUB), University of Barcelona, Avda Diagonal 645, E-08028 Barcelona, Spain"},{"name":"CIBER Fisiopatologia de la Obesidad y Nutrici\u00f3n, Instituto de Salud Carlos III, Avda Diagonal 645, E-08028, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Villarroya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, and Institute of Biomedicine (IBUB), University of Barcelona, Avda Diagonal 645, E-08028 Barcelona, Spain"},{"name":"Hospital de la Santa Creu I Sant Pau, Autonomous University of Barcelona and Red de Investigaci\u00f3n en SIDA (RIS), Avda Sant Antoni M. 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