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dc.contributor.author
David, Sebastián
dc.contributor.author
Sorianello, Eleonora Mariana
dc.contributor.author
Segalés, Jessica
dc.contributor.author
Irazoki, Andrea
dc.contributor.author
Ruiz Bonilla, Vanessa
dc.contributor.author
Sala, David
dc.contributor.author
Planet, Evarist
dc.contributor.author
Berenguer Llergo, Antoni
dc.contributor.author
Muñoz, Juan Pablo
dc.contributor.author
Sánchez Feutrie, Manuela
dc.contributor.author
Plana, Natàlia
dc.contributor.author
Hernández Álvarez, María Isabel
dc.contributor.author
Serrano, Antonio L.
dc.contributor.author
Palacín, Manuel
dc.contributor.author
Zorzano, Antonio
dc.date.available
2017-06-14T15:47:06Z
dc.date.issued
2016-08
dc.identifier.citation
David, Sebastián; Sorianello, Eleonora Mariana; Segalés, Jessica; Irazoki, Andrea; Ruiz Bonilla, Vanessa; et al.; Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway; Nature Publishing Group; Embo Journal; 35; 8-2016; 1677-1693
dc.identifier.issn
0261-4189
dc.identifier.uri
http://hdl.handle.net/11336/18160
dc.description.abstract
Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Aging
dc.subject
Mitofusin 2
dc.subject
Mitochondria
dc.subject
Autophagy
dc.subject
Sarcopenia
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-12T21:00:29Z
dc.identifier.eissn
1460-2075
dc.journal.volume
35
dc.journal.pagination
1677-1693
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: David, Sebastián. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Sorianello, Eleonora Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Segalés, Jessica. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Irazoki, Andrea. IRB Barcelona; España
dc.description.fil
Fil: Ruiz Bonilla, Vanessa. Universitat Pompeu Fabra; España
dc.description.fil
Fil: Sala, David. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Planet, Evarist. IRB Barcelona; España
dc.description.fil
Fil: Berenguer Llergo, Antoni. IRB Barcelona; España
dc.description.fil
Fil: Muñoz, Juan Pablo. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Sánchez Feutrie, Manuela. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Plana, Natàlia. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Hernández Álvarez, María Isabel. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Serrano, Antonio L.. Universitat Pompeu Fabra; España
dc.description.fil
Fil: Palacín, Manuel. Universitat Autonoma de Barcelona; España
dc.description.fil
Fil: Zorzano, Antonio. Universitat Autonoma de Barcelona; España
dc.journal.title
Embo Journal
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://emboj.embopress.org/content/35/15/1677
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.15252/embj.201593084
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