Show simple item record

dc.contributor.authorHiona, Asimina
dc.contributor.authorSanz, Alberto
dc.contributor.authorKujoth, Gregory C.
dc.contributor.authorPamplona Gras, Reinald
dc.contributor.authorSeo, Arnold Y.
dc.contributor.authorHofer, Tim
dc.contributor.authorSomeya, Shinichi
dc.contributor.authorMiyakawa, Takuya
dc.contributor.authorNakayama, Chie
dc.contributor.authorSamhan-Arias, Alejandro K.
dc.contributor.authorServais, Stephane
dc.contributor.authorBarger, Jamie L.
dc.contributor.authorPortero Otín, Manuel
dc.contributor.authorTanokura, Masaru
dc.contributor.authorProlla, Tomas A.
dc.contributor.authorLeeuwenburgh, Christiaan
dc.date.accessioned2011-02-04T13:14:44Z
dc.date.available2011-02-04T13:14:44Z
dc.date.issued2010
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10459.1/30325
dc.description.abstractBackground: Aging results in a progressive loss of skeletal muscle, a condition known as sarcopenia. Mitochondrial DNA (mtDNA) mutations accumulate with aging in skeletal muscle and correlate with muscle loss, although no causal relationship has been established. Methodology/Principal Findings: We investigated the relationship between mtDNA mutations and sarcopenia at the gene expression and biochemical levels using a mouse model that expresses a proofreading-deficient version (D257A) of the mitochondrial DNA Polymerase c, resulting in increased spontaneous mtDNA mutation rates. Gene expression profiling of D257A mice followed by Parametric Analysis of Gene Set Enrichment (PAGE) indicates that the D257A mutation is associated with a profound downregulation of gene sets associated with mitochondrial function. At the biochemical level, sarcopenia in D257A mice is associated with a marked reduction (35–50%) in the content of electron transport chain (ETC) complexes I, III and IV, all of which are partly encoded by mtDNA. D257A mice display impaired mitochondrial bioenergetics associated with compromised state-3 respiration, lower ATP content and a resulting decrease in mitochondrial membrane potential (Dym). Surprisingly, mitochondrial dysfunction was not accompanied by an increase in mitochondrial reactive oxygen species (ROS) production or oxidative damage. Conclusions/Significance: These findings demonstrate that mutations in mtDNA can be causal in sarcopenia by affecting the assembly of functional ETC complexes, the lack of which provokes a decrease in oxidative phosphorylation, without an increase in oxidative stress, and ultimately, skeletal muscle apoptosis and sarcopenia.ca_ES
dc.language.isoengca_ES
dc.publisherPublic Library of Science (PLoS)ca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1371/journal.pone.0011468ca_ES
dc.relation.ispartofPLoS ONE, 2010, vol. 5, núm. 7, e11468ca_ES
dc.rightscc-by, (c) Hiona et al., 2010ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/es/deed.caca_ES
dc.subject.otherADN mitocondrialca_ES
dc.subject.otherMutació (Biologia)ca_ES
dc.titleMitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator miceca_ES
dc.typearticleca_ES
dc.identifier.idgrec015605
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsopen access
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0011468


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

cc-by, (c) Hiona et al., 2010
Except where otherwise noted, this item's license is described as cc-by, (c) Hiona et al., 2010