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Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus

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 under...

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Autores principales: Juárez-Flores, Diana Luz, Ezquerra, Mario, Gonzàlez-Casacuberta, ïngrid, Ormazabal, Aida, Morén, Constanza, Tolosa, Eduardo, Fucho, Raquel, Guitart-Mampel, Mariona, Casado, Mercedes, Valldeoriola, Francesc, de la Torre-Lara, Joan, Muñoz, Esteban, Tobías, Ester, Compta, Yaroslau, García-García, Francesc Josep, García-Ruiz, Carmen, Fernandez-Checa, Jose Carlos, Martí, Maria José, Grau, Josep Maria, Cardellach, Francesc, Artuch, Rafael, Fernández-Santiago, Rubén, Garrabou, Glòria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693963/
https://www.ncbi.nlm.nih.gov/pubmed/33143119
http://dx.doi.org/10.3390/antiox9111063
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author Juárez-Flores, Diana Luz
Ezquerra, Mario
Gonzàlez-Casacuberta, ïngrid
Ormazabal, Aida
Morén, Constanza
Tolosa, Eduardo
Fucho, Raquel
Guitart-Mampel, Mariona
Casado, Mercedes
Valldeoriola, Francesc
de la Torre-Lara, Joan
Muñoz, Esteban
Tobías, Ester
Compta, Yaroslau
García-García, Francesc Josep
García-Ruiz, Carmen
Fernandez-Checa, Jose Carlos
Martí, Maria José
Grau, Josep Maria
Cardellach, Francesc
Artuch, Rafael
Fernández-Santiago, Rubén
Garrabou, Glòria
author_facet Juárez-Flores, Diana Luz
Ezquerra, Mario
Gonzàlez-Casacuberta, ïngrid
Ormazabal, Aida
Morén, Constanza
Tolosa, Eduardo
Fucho, Raquel
Guitart-Mampel, Mariona
Casado, Mercedes
Valldeoriola, Francesc
de la Torre-Lara, Joan
Muñoz, Esteban
Tobías, Ester
Compta, Yaroslau
García-García, Francesc Josep
García-Ruiz, Carmen
Fernandez-Checa, Jose Carlos
Martí, Maria José
Grau, Josep Maria
Cardellach, Francesc
Artuch, Rafael
Fernández-Santiago, Rubén
Garrabou, Glòria
author_sort Juárez-Flores, Diana Luz
collection PubMed
description 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.
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spelling pubmed-76939632020-11-28 Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus Juárez-Flores, Diana Luz Ezquerra, Mario Gonzàlez-Casacuberta, ïngrid Ormazabal, Aida Morén, Constanza Tolosa, Eduardo Fucho, Raquel Guitart-Mampel, Mariona Casado, Mercedes Valldeoriola, Francesc de la Torre-Lara, Joan Muñoz, Esteban Tobías, Ester Compta, Yaroslau García-García, Francesc Josep García-Ruiz, Carmen Fernandez-Checa, Jose Carlos Martí, Maria José Grau, Josep Maria Cardellach, Francesc Artuch, Rafael Fernández-Santiago, Rubén Garrabou, Glòria Antioxidants (Basel) Article 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. MDPI 2020-10-30 /pmc/articles/PMC7693963/ /pubmed/33143119 http://dx.doi.org/10.3390/antiox9111063 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Juárez-Flores, Diana Luz
Ezquerra, Mario
Gonzàlez-Casacuberta, ïngrid
Ormazabal, Aida
Morén, Constanza
Tolosa, Eduardo
Fucho, Raquel
Guitart-Mampel, Mariona
Casado, Mercedes
Valldeoriola, Francesc
de la Torre-Lara, Joan
Muñoz, Esteban
Tobías, Ester
Compta, Yaroslau
García-García, Francesc Josep
García-Ruiz, Carmen
Fernandez-Checa, Jose Carlos
Martí, Maria José
Grau, Josep Maria
Cardellach, Francesc
Artuch, Rafael
Fernández-Santiago, Rubén
Garrabou, Glòria
Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus
title Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus
title_full Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus
title_fullStr Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus
title_full_unstemmed Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus
title_short Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus
title_sort disrupted mitochondrial and metabolic plasticity underlie comorbidity between age-related and degenerative disorders as parkinson disease and type 2 diabetes mellitus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693963/
https://www.ncbi.nlm.nih.gov/pubmed/33143119
http://dx.doi.org/10.3390/antiox9111063
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