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dc.contributor.authorOst, Mario
dc.contributor.authorKeipert, Susanne
dc.contributor.authorSchothorst, Evert M. van
dc.contributor.authorDonner, Verena
dc.contributor.authorStelt, Inge van der
dc.contributor.authorKipp, Anna P.
dc.contributor.authorPetzke, Klaus-Jürgen
dc.contributor.authorJové Font, Mariona
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorKeijer, Jaap
dc.contributor.authorKlaus, Susanne
dc.date.accessioned2016-11-10T08:25:25Z
dc.date.issued2014
dc.identifier.issn0892-6638
dc.identifier.urihttp://hdl.handle.net/10459.1/58448
dc.description.abstractRecent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPH-generating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stress-signaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.—Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K.-J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., Klaus, S. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux.ca_ES
dc.description.sponsorshipThis research received funding from the European Union’s Seventh Framework Program FP7 2007–2013 under Grant Agreement 244995 (BIOCLAIMS Project) and from the Leibniz Society (SAW-2013-FBN-3) as well as grants from the Spanish Ministry of Economy and Competitiveness (PI13/ 00584, PI11/01532) and the Generalitat of Catalounya (2014SGR168).
dc.language.isoengca_ES
dc.publisherFASEBca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1096/fj.14-261503ca_ES
dc.relation.ispartofFASEB Journal, 2014, vol. 29, núm. 4, p. 1314-1328ca_ES
dc.rights(c) FASEB, 2014ca_ES
dc.subjectAmino acid metabolismca_ES
dc.subjectMetabolic reprogrammingca_ES
dc.subjectMitochondrial myopathyca_ES
dc.subjectOxidative stressca_ES
dc.titleMuscle mitohormesis promotes cellular survival via serine/glycine pathway fluxca_ES
dc.typearticleca_ES
dc.identifier.idgrec023681
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1096/fj.14-261503
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/244995
dc.date.embargoEndDate2025-01-01


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