Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/174324
Title: Disrupted mitochondrial and metabolic plasticity underlie comorbidity between age-Related and degenerative disorders as parkinson disease and type 2 diabetes mellitus.
Author: Juárez Flores, Diana Luz
Ezquerra, Mario
González Casacuberta, Ingrid
Ormazabal Herrero, Aida
Morén Núñez, Constanza
Tolosa, Eduardo
Fucho Salvador, Raquel
Guitart Mampel, Mariona
Casado, Mercedes
Valldeoriola Serra, Francesc
Torre Lara, Joan de la
Muñoz García, José Esteban
Tobías Baraja, Ester
Compta, Yaroslau
García García, Francesc J.
García Ruiz, Carmen
Fernández Checa Torres, José Carlos
Martí, Maria J.
Grau Junyent, Josep M. (Josep Maria)
Cardellach, Francesc
Artuch Iriberri, Rafael
Fernández Santiago, Rubén
Garrabou Tornos, Glòria
Keywords: Malaltia de Parkinson
Diabetis
Comorbiditat
Mitocondris
Parkinson's disease
Diabetes
Comorbidity
Mitochondria
Issue Date: 30-Oct-2020
Publisher: MDPI
Abstract: Idiopathic Parkinson's disease (iPD) and type 2 diabetes mellitus (T2DM) are chronic, multisystemic, and degenerative diseases associated with aging, with eventual epidemiological co-morbidity and overlap in molecular basis. This study aims to explore if metabolic and mitochondrial alterations underlie the previously reported epidemiologic and clinical co-morbidity from a molecular level. To evaluate the adaptation of iPD to a simulated pre-diabetogenic state, we exposed primary cultured fibroblasts from iPD patients and controls to standard (5 mM) and high (25 mM) glucose concentrations to further characterize metabolic and mitochondrial resilience. iPD fibroblasts showed increased organic and amino acid levels related to mitochondrial metabolism with respect to controls, and these differences were enhanced in high glucose conditions (citric, suberic, and sebacic acids levels increased, as well as alanine, glutamate, aspartate, arginine, and ornithine amino acids; p-values between 0.001 and 0.05). The accumulation of metabolites in iPD fibroblasts was associated with (and probably due to) the concomitant mitochondrial dysfunction observed at enzymatic, oxidative, respiratory, and morphologic level. Metabolic and mitochondrial plasticity of controls was not observed in iPD fibroblasts, which were unable to adapt to different glucose conditions. Impaired metabolism and mitochondrial activity in iPD may limit energy supply for cell survival. Moreover, reduced capacity to adapt to disrupted glucose balance characteristic of T2DM may underlay the co-morbidity between both diseases. Conclusions: Fibroblasts from iPD patients showed mitochondrial impairment, resulting in the accumulation of organic and amino acids related to mitochondrial metabolism, especially when exposed to high glucose. Mitochondrial and metabolic defects down warding cell plasticity to adapt to changing glucose bioavailability may explain the comorbidity between iPD and T2DM.
Note: Reproducció del document publicat a: https://doi.org/10.3390/antiox9111063
It is part of: Antioxidants, 2020, vol. 9, num. 11
URI: http://hdl.handle.net/2445/174324
Related resource: https://doi.org/10.3390/antiox9111063
ISSN: 2076-3921
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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