Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/176797
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Degradation of altered mitochondria by autophagy is impaired in Lafora disease |
Autor: | Lahuerta, Marcos CSIC; Aguado, Carmen; Sánchez-Martín, Pablo CSIC ORCID; Sanz, Pascual CSIC ORCID ; Knecht, Erwin | Palabras clave: | Lafora disease Autophagy Human fibroblasts Mitochondria Mitophagy |
Fecha de publicación: | jun-2018 | Editor: | Wiley-Blackwell Federation of European Biochemical Societies |
Citación: | FEBS Journal 285(11):2071-2090 (2018) | Resumen: | Lafora disease (LD) is a fatal neurodegenerative disorder caused mostly by mutations in either of two genes encoding laforin and malin. LD is characterized by accumulation of a poorly branched form of glycogen in the cytoplasm of neurons and other cells. We previously reported dysfunctional mitochondria in different LD models. Now, using mitochondrial uncouplers and respiratory chain inhibitors, we have investigated with human fibroblasts a possible alteration in the selective degradation of damaged mitochondria (mitophagy) in LD. By flow cytometry of MitoTracker-labelled cells and measuring the levels of various mitochondrial proteins by western blot, we found in LD fibroblasts a partial impairment in the increased mitochondrial degradation produced by these treatments. In addition, colocalization of mitochondrial and lysosomal markers decreased in LD fibroblasts. All these results are consistent with a partial impairment in the induced autophagic degradation of dysfunctional mitochondria in LD fibroblasts. However, canonical recruitment of Parkin to mitochondria under these conditions remained unaffected in LD fibroblasts, and also in SH-SY5Y cells after malin and laforin overexpression. Neither mitochondrial localization nor protein levels of Bcl-2-like protein 13, another component of the mitophagic machinery that operates under these conditions, were affected in LD fibroblasts. In contrast, although these treatments raised autophagy in both control and LD fibroblasts, this enhanced autophagy was clearly lower in the latter cells. Therefore, the autophagic degradation of altered mitochondria is impaired in LD, which is due to a partial defect in the autophagic response and not in the canonical mitophagy signalling pathways. | Descripción: | 20 páginas, 13 figuras | Versión del editor: | http://dx.doi.org/10.1111/febs.14468 | URI: | http://hdl.handle.net/10261/176797 | DOI: | 10.1111/febs.14468 | ISSN: | 1742-464X | E-ISSN: | 1742-4658 |
Aparece en las colecciones: | (IBV) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
2018 FEBS J 285-2071 Author Copy.pdf | 7,61 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
18
checked on 13-may-2024
SCOPUSTM
Citations
23
checked on 06-may-2024
WEB OF SCIENCETM
Citations
22
checked on 23-feb-2024
Page view(s)
265
checked on 12-may-2024
Download(s)
243
checked on 12-may-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.