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Title: Mitochondrial and autophagic alterations in skin fibroblasts from Parkinson disease patients with Parkin mutations.
Author: González Casacuberta, Ingrid
Juárez Flores, Diana Luz
Ezquerra, Mario
Fucho Salvador, Raquel
Catalán García, Marc
Guitart Mampel, Mariona
Tobías Baraja, Ester
García Ruiz, Carmen
Fernández Santiago, Rubén
Tolosa, Eduardo
Martí, Maria José
Grau Junyent, Josep M. (Josep Maria)
Fernández Checa Torres, José Carlos
Cardellach, Francesc
Morén Núñez, Constanza
Garrabou Tornos, Glòria
Keywords: Malaltia de Parkinson
Parkinson's disease
Issue Date: 9-Jun-2019
Publisher: Impact Journals
Abstract: 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.
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It is part of: Aging, 2019, vol. 11, num. 11, p. 3750-3767
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ISSN: 1945-4589
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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