Coenzyme Q deficiency triggers mitochondria degradation by mitophagy
Coenzyme Q(10) (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...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2009 |
| País: | España |
| Institución: | Fundació Sant Joan de Déu |
| Repositorio: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p1444 |
| Acceso en línea: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1444 |
| Access Level: | acceso abierto |
| Palabra clave: | autophagy coenzyme Q free radicals mitochondria mitochondrial disease mitochondrial permeability transition mitophagy |
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Coenzyme Q deficiency triggers mitochondria degradation by mitophagyRodríguez-Hernández ACordero MDSalviati LArtuch RPineda MBriones PGómez Izquierdo LCotán DNavas PSánchez-Alcázar JAautophagycoenzyme Qfree radicalsmitochondriamitochondrial diseasemitochondrial permeability transitionmitophagyCoenzyme Q(10) (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 four patients with CoQ deficiency. Assays of cultured fibroblasts revealed decreased activities of complex II + III, complex III and complex TV, 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 (P-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.TAYLOR & FRANCIS INC2009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1444AutophagyISSN: 15548627ISSNe: 15548635reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p14442026-05-27T12:37:41Z |
| 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 A autophagy coenzyme Q free radicals mitochondria mitochondrial disease 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 A Cordero MD Salviati L Artuch R Pineda M Briones P Gómez Izquierdo L Cotán D Navas P Sánchez-Alcázar JA |
| author |
Rodríguez-Hernández A |
| author_facet |
Rodríguez-Hernández A Cordero MD Salviati L Artuch R Pineda M Briones P Gómez Izquierdo L Cotán D Navas P Sánchez-Alcázar JA |
| author_role |
author |
| author2 |
Cordero MD Salviati L Artuch R Pineda M Briones P Gómez Izquierdo L Cotán D Navas P Sánchez-Alcázar JA |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
autophagy coenzyme Q free radicals mitochondria mitochondrial disease mitochondrial permeability transition mitophagy |
| topic |
autophagy coenzyme Q free radicals mitochondria mitochondrial disease mitochondrial permeability transition mitophagy |
| description |
Coenzyme Q(10) (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 four patients with CoQ deficiency. Assays of cultured fibroblasts revealed decreased activities of complex II + III, complex III and complex TV, 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 (P-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. |
| publishDate |
2009 |
| dc.date.none.fl_str_mv |
2009 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1444 |
| url |
https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=1444 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
TAYLOR & FRANCIS INC |
| publisher.none.fl_str_mv |
TAYLOR & FRANCIS INC |
| dc.source.none.fl_str_mv |
Autophagy ISSN: 15548627 ISSNe: 15548635 reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname:Fundació Sant Joan de Déu |
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Fundació Sant Joan de Déu |
| reponame_str |
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
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r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
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1869404903679459328 |
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15,812429 |