Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.

PRKN encodes an E3-ubiquitin-ligase involved in multiple cell processes including mitochondrial homeostasis and autophagy. Previous studies reported alterations of mitochondrial function in fibroblasts from patients with PRKN mutation-associated Parkinson's disease (PRKN-PD) but have been only...

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Autores: González Casacuberta, Ingrid, Juárez Flores, Diana Luz, Ezquerra Trabalón, Mario, Fucho Salvador, Raquel, Catalán García, Marc, Guitart Mampel, Mariona, Tobías, Ester, García Ruiz, Carmen, Fernández Santiago, Rubén, Tolosa, Eduardo, Martí Domènech, Ma. Josep, Grau Junyent, Josep M. (Josep Maria), Fernández Checa Torres, José Carlos, Cardellach, Francesc, Morén Núñez, Constanza, Garrabou Tornos, Glòria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/179115
Acceso en línea:https://hdl.handle.net/2445/179115
Access Level:acceso abierto
Palabra clave:Malaltia de Parkinson
Pell
Parkinson's disease
Skin
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spelling Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.González Casacuberta, IngridJuárez Flores, Diana LuzEzquerra Trabalón, MarioFucho Salvador, RaquelCatalán García, MarcGuitart Mampel, MarionaTobías, EsterGarcía Ruiz, CarmenFernández Santiago, RubénTolosa, EduardoMartí Domènech, Ma. JosepGrau Junyent, Josep M. (Josep Maria)Fernández Checa Torres, José CarlosCardellach, FrancescMorén Núñez, ConstanzaGarrabou Tornos, GlòriaMalaltia de ParkinsonPellParkinson's diseaseSkinPRKN encodes an E3-ubiquitin-ligase involved in multiple cell processes including mitochondrial homeostasis and autophagy. Previous studies reported alterations of mitochondrial function in fibroblasts from patients with PRKN mutation-associated Parkinson's disease (PRKN-PD) but have been only conducted in glycolytic conditions, potentially masking mitochondrial alterations. Additionally, autophagy flux studies in this cell model are missing.We analyzed mitochondrial function and autophagy in PRKN-PD skin-fibroblasts (n=7) and controls (n=13) in standard (glucose) and mitochondrial-challenging (galactose) conditions.In glucose, PRKN-PD fibroblasts showed preserved mitochondrial bioenergetics with trends to abnormally enhanced mitochondrial respiration that, accompanied by decreased CI, may account for the increased oxidative stress. In galactose, PRKN-PD fibroblasts exhibited decreased basal/maximal respiration vs. controls and reduced mitochondrial CIV and oxidative stress compared to glucose, suggesting an inefficient mitochondrial oxidative capacity to meet an extra metabolic requirement. PRKN-PD fibroblasts presented decreased autophagic flux with reduction of autophagy substrate and autophagosome synthesis in both conditions.The alterations exhibited under neuron-like oxidative environment (galactose), may be relevant to the disease pathogenesis potentially explaining the increased susceptibility of dopaminergic neurons to undergo degeneration. Abnormal PRKN-PD phenotype supports the usefulness of fibroblasts to model disease and the view of PD as a systemic disease where molecular alterations are present in peripheral tissues.Impact Journals2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/179115Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.18632/aging.102014Aging, 2019, vol. 11, num. 11, p. 3750-3767https://doi.org/10.18632/aging.102014cc-by (c) González Casacuberta, Ingrid et al., 2019https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1791152026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
title Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
spellingShingle Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
González Casacuberta, Ingrid
Malaltia de Parkinson
Pell
Parkinson's disease
Skin
title_short Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
title_full Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
title_fullStr Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
title_full_unstemmed Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
title_sort Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
dc.creator.none.fl_str_mv González Casacuberta, Ingrid
Juárez Flores, Diana Luz
Ezquerra Trabalón, Mario
Fucho Salvador, Raquel
Catalán García, Marc
Guitart Mampel, Mariona
Tobías, Ester
García Ruiz, Carmen
Fernández Santiago, Rubén
Tolosa, Eduardo
Martí Domènech, Ma. Josep
Grau Junyent, Josep M. (Josep Maria)
Fernández Checa Torres, José Carlos
Cardellach, Francesc
Morén Núñez, Constanza
Garrabou Tornos, Glòria
author González Casacuberta, Ingrid
author_facet González Casacuberta, Ingrid
Juárez Flores, Diana Luz
Ezquerra Trabalón, Mario
Fucho Salvador, Raquel
Catalán García, Marc
Guitart Mampel, Mariona
Tobías, Ester
García Ruiz, Carmen
Fernández Santiago, Rubén
Tolosa, Eduardo
Martí Domènech, Ma. Josep
Grau Junyent, Josep M. (Josep Maria)
Fernández Checa Torres, José Carlos
Cardellach, Francesc
Morén Núñez, Constanza
Garrabou Tornos, Glòria
author_role author
author2 Juárez Flores, Diana Luz
Ezquerra Trabalón, Mario
Fucho Salvador, Raquel
Catalán García, Marc
Guitart Mampel, Mariona
Tobías, Ester
García Ruiz, Carmen
Fernández Santiago, Rubén
Tolosa, Eduardo
Martí Domènech, Ma. Josep
Grau Junyent, Josep M. (Josep Maria)
Fernández Checa Torres, José Carlos
Cardellach, Francesc
Morén Núñez, Constanza
Garrabou Tornos, Glòria
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia de Parkinson
Pell
Parkinson's disease
Skin
topic Malaltia de Parkinson
Pell
Parkinson's disease
Skin
description PRKN encodes an E3-ubiquitin-ligase involved in multiple cell processes including mitochondrial homeostasis and autophagy. Previous studies reported alterations of mitochondrial function in fibroblasts from patients with PRKN mutation-associated Parkinson's disease (PRKN-PD) but have been only conducted in glycolytic conditions, potentially masking mitochondrial alterations. Additionally, autophagy flux studies in this cell model are missing.We analyzed mitochondrial function and autophagy in PRKN-PD skin-fibroblasts (n=7) and controls (n=13) in standard (glucose) and mitochondrial-challenging (galactose) conditions.In glucose, PRKN-PD fibroblasts showed preserved mitochondrial bioenergetics with trends to abnormally enhanced mitochondrial respiration that, accompanied by decreased CI, may account for the increased oxidative stress. In galactose, PRKN-PD fibroblasts exhibited decreased basal/maximal respiration vs. controls and reduced mitochondrial CIV and oxidative stress compared to glucose, suggesting an inefficient mitochondrial oxidative capacity to meet an extra metabolic requirement. PRKN-PD fibroblasts presented decreased autophagic flux with reduction of autophagy substrate and autophagosome synthesis in both conditions.The alterations exhibited under neuron-like oxidative environment (galactose), may be relevant to the disease pathogenesis potentially explaining the increased susceptibility of dopaminergic neurons to undergo degeneration. Abnormal PRKN-PD phenotype supports the usefulness of fibroblasts to model disease and the view of PD as a systemic disease where molecular alterations are present in peripheral tissues.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/179115
url https://hdl.handle.net/2445/179115
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.18632/aging.102014
Aging, 2019, vol. 11, num. 11, p. 3750-3767
https://doi.org/10.18632/aging.102014
dc.rights.none.fl_str_mv cc-by (c) González Casacuberta, Ingrid et al., 2019
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) González Casacuberta, Ingrid et al., 2019
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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