Coenzyme Q deficiency triggers mitochondria degradation by mitophagy

14 páginas, 11 figuras, 1 tabla.

Detalles Bibliográficos
Autores: Rodríguez-Hernández, Ángeles, Cordero, Mario D., Salviati, Leonardo, Artuch, Rafael, Pineda, Mercé, Briones, Paz, Gómez Izquierdo, Lourdes, Cotán, David, Navas, Plácido, Sánchez-Alcázar, José Antonio
Tipo de recurso: artículo
Fecha de publicación:2009
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/40287
Acceso en línea:http://hdl.handle.net/10261/40287
Access Level:acceso abierto
Palabra clave:Autophagy
Coenzyme Q
Free radicals
Mitochondria
Mitochondrial diseases
Mitochondrial permeability transition
Mitophagy
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spelling Coenzyme Q deficiency triggers mitochondria degradation by mitophagyRodríguez-Hernández, ÁngelesCordero, Mario D.Salviati, LeonardoArtuch, RafaelPineda, MercéBriones, PazGómez Izquierdo, LourdesCotán, DavidNavas, PlácidoSánchez-Alcázar, José AntonioAutophagyCoenzyme QFree radicalsMitochondriaMitochondrial diseasesMitochondrial permeability transitionMitophagy14 páginas, 11 figuras, 1 tabla.Coenzyme Q10 (CoQ) is a small lipophilic molecule critical for the transport of electrons from complexes I and II to complex III in the mitochondrial respiratory chain. CoQ deficiency is a rare human genetic condition that has been associated with a variety of clinical phenotypes. With the aim of elucidating how CoQ deficiency affects an organism, we have investigated the pathophysiologic processes present within fibroblasts derived from 4 patients with CoQ deficiency. Assays of cultured fibroblasts revealed decreased activities of complex II+III, complex III, and complex IV, reduced expression of mitochondrial proteins involved in oxidative phosphorylation, decreased mitochondrial membrane potential, increased production of reactive oxygen species (ROS), activation of mitochondrial permeability transition (MPT), and reduced growth rates. These abnormalities were partially restored by CoQ supplementation. Moreover, we demonstrate that CoQ deficient fibroblasts exhibited increased levels of lysosomal markers (β-galactosidase, cathepsin, LC3, and Lyso Tracker), and enhanced expression of autophagic genes at both transcriptional and translational levels, indicating the presence of autophagy. Electron microscopy studies confirmed a massive degradation of the altered mitochondria by mitophagy. Autophagy in CoQ deficient fibroblasts was abolished by antioxidants or cyclosporin treatments suggesting that both ROS and MPT participate in this process. Furthermore, prevention of autophagy in CoQ deficient fibroblasts by 3-methyl adenine or wortmannin, as well as the induction of CoQ deficiency in cells lacking autophagy (by means of genetic knockout of the Atg5 gene in mouse embryonic fibroblasts) resulted in apoptotic cell death, suggesting a protective role of autophagy in CoQ deficiency.This work was supported by grants PI041617 from the FIS, Ministerio de Sanidad, Spain, and European Union contract LSHBCT-2004-005151 (UBIGENES). This group is founded by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII.Peer reviewedLandes Bioscience201120112009info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/40287reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.4161/auto.5.1.7174info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/402872026-05-22T06:33:51Z
dc.title.none.fl_str_mv Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
title Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
spellingShingle Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
Rodríguez-Hernández, Ángeles
Autophagy
Coenzyme Q
Free radicals
Mitochondria
Mitochondrial diseases
Mitochondrial permeability transition
Mitophagy
title_short Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
title_full Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
title_fullStr Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
title_full_unstemmed Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
title_sort Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
dc.creator.none.fl_str_mv Rodríguez-Hernández, Ángeles
Cordero, Mario D.
Salviati, Leonardo
Artuch, Rafael
Pineda, Mercé
Briones, Paz
Gómez Izquierdo, Lourdes
Cotán, David
Navas, Plácido
Sánchez-Alcázar, José Antonio
author Rodríguez-Hernández, Ángeles
author_facet Rodríguez-Hernández, Ángeles
Cordero, Mario D.
Salviati, Leonardo
Artuch, Rafael
Pineda, Mercé
Briones, Paz
Gómez Izquierdo, Lourdes
Cotán, David
Navas, Plácido
Sánchez-Alcázar, José Antonio
author_role author
author2 Cordero, Mario D.
Salviati, Leonardo
Artuch, Rafael
Pineda, Mercé
Briones, Paz
Gómez Izquierdo, Lourdes
Cotán, David
Navas, Plácido
Sánchez-Alcázar, José Antonio
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autophagy
Coenzyme Q
Free radicals
Mitochondria
Mitochondrial diseases
Mitochondrial permeability transition
Mitophagy
topic Autophagy
Coenzyme Q
Free radicals
Mitochondria
Mitochondrial diseases
Mitochondrial permeability transition
Mitophagy
description 14 páginas, 11 figuras, 1 tabla.
publishDate 2009
dc.date.none.fl_str_mv 2009
2011
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/40287
url http://hdl.handle.net/10261/40287
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.4161/auto.5.1.7174
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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