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dc.contributor.authorCotán, David-
dc.contributor.authorCordero, Mario D.-
dc.contributor.authorGarrido-Maraver, Juan-
dc.contributor.authorOropesa-Ávila, Manuel-
dc.contributor.authorRodríguez-Hernández, Ángeles-
dc.contributor.authorGómez Izquierdo, Lourdes-
dc.contributor.authorMata, Mario de la-
dc.contributor.authorMiguel, Manuel de-
dc.contributor.authorBautista Lorite, Juan-
dc.contributor.authorRivas Infante, Eloy-
dc.contributor.authorJackson, Sandra-
dc.contributor.authorNavas, Plácido-
dc.contributor.authorSánchez-Alcázar, José Antonio-
dc.date.accessioned2011-10-17T11:05:47Z-
dc.date.available2011-10-17T11:05:47Z-
dc.date.issued2011-05-06-
dc.identifier.citationFASEB Journal 25(8): 2669-2687 (2011)es_ES
dc.identifier.issn0892-6638-
dc.identifier.otherPMID: 21551238-
dc.identifier.urihttp://hdl.handle.net/10261/41221-
dc.description9 páginas.es_ES
dc.description.abstractMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mtDNA. Here, we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from 2 patients with MELAS who harbored the A3243G mutation. Both mitochondrial respiratory chain enzyme activities and coenzyme Q(10) (CoQ) levels were significantly decreased in MELAS fibroblasts. A similar decrease in mitochondrial membrane potential was found in intact MELAS fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and the activation of mitochondrial permeability transition (MPT), which triggered the degradation of impaired mitochondria. Furthermore, we found defective autophagosome elimination in MELAS fibroblasts. Electron and fluorescence microscopy studies confirmed a massive degradation of mitochondria and accumulation of autophagosomes, suggesting mitophagy activation and deficient autophagic flux. Transmitochondrial cybrids harboring the A3243G mutation also showed CoQ deficiency and increased autophagy activity. All these abnormalities were partially restored by CoQ supplementation. Autophagy in MELAS fibroblasts was also abolished by treatment with antioxidants or cyclosporine, suggesting that both reactive oxygen species and MPT participate in this process. Furthermore, prevention of autophagy in MELAS fibroblasts resulted in apoptotic cell death, suggesting a protective role of autophagy in MELAS fibroblasts.es_ES
dc.description.sponsorshipThis work was supported by Ministerio de Sanidad, Spain, grants FIS PI080500 and FIS EC08/00076, and by Asociación de Enfermos de Patología Mitocondrial (AEPMI) and Fundación Española de Enfermedades Lisosomales (FEEL). M. de la Mata is the recipient of a fellowship from Colegio Oficial de Farmacéuticos de Sevilla. This group was founded by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII).-
dc.language.isoenges_ES
dc.publisherFederation of American Societies for Experimental Biologyes_ES
dc.rightsclosedAccesses_ES
dc.subjectAutophagyes_ES
dc.subjectFree radicalses_ES
dc.subjectMitochondrial diseaseses_ES
dc.subjectElectron transportes_ES
dc.subjectFibroblastses_ES
dc.subjectMELAS syndromees_ES
dc.subjectMicrotubule-associated proteinses_ES
dc.subjectUbiquinonees_ES
dc.titleSecondary coenzyme Q10 deficiency triggers mitochondria degradation by mitophagy in MELAS fibroblastses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1096/fj.10-165340-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1096/fj.10-165340es_ES
dc.identifier.e-issn1530-6860-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderMinisterio de Sanidad y Consumo (España)-
dc.contributor.funderAsociación de Enfermos de Patologías Mitocondriales (España)-
dc.contributor.funderReal e Ilustre Colegio de Farmacéuticos de Sevilla-
dc.contributor.funderCentro de Investigación Biomédica en Red Enfermedades Raras (España)-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
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