{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:28:47Z","timestamp":1787066927792,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Integrated Projects of Excellence (PIE)","award":["PIE14\/00061"],"award-info":[{"award-number":["PIE14\/00061"]}]},{"name":"Fondo de Investigaciones Sanitarias del ISCIII","award":["PI1800498"],"award-info":[{"award-number":["PI1800498"]}]},{"name":"Fondo de Investigaciones Sanitarias del ISCIII","award":["PI1800451"],"award-info":[{"award-number":["PI1800451"]}]},{"name":"Fundaci\u00f3 Privada Cellex and Suports de Grups de Recerca","award":["2017 SGR 893"],"award-info":[{"award-number":["2017 SGR 893"]}]},{"name":"Maria de Maetzu Unit of Excellence","award":["MDM-2017-0729"],"award-info":[{"award-number":["MDM-2017-0729"]}]},{"name":"Retos de investigaci\u00f3n. Ministerio de Ciencia, Innovaci\u00f3n y Universidades (ES).","award":["SAF2017-85877-R"],"award-info":[{"award-number":["SAF2017-85877-R"]}]},{"name":"Retos de investigaci\u00f3n. Ministerio de Ciencia, Innovaci\u00f3n y Universidades (ES)","award":["SAF2015-69944-R"],"award-info":[{"award-number":["SAF2015-69944-R"]}]},{"name":"Proyectos I+D+i. Ministerio de Ciencia, Innovaci\u00f3n y Universidades (ES)","award":["PID2019-111669RB-I00"],"award-info":[{"award-number":["PID2019-111669RB-I00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Idiopathic Parkinson\u2019s 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.<\/jats:p>","DOI":"10.3390\/antiox9111063","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T09:29:32Z","timestamp":1604050172000},"page":"1063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Disrupted Mitochondrial and Metabolic Plasticity Underlie Comorbidity between Age-Related and Degenerative Disorders as Parkinson Disease and Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"9","author":[{"given":"Diana Luz","family":"Ju\u00e1rez-Flores","sequence":"first","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Ezquerra","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS, Institut de Neuroci\u00e8ncies, UB, 08036 Barcelona, Spain"},{"name":"Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06\/05\/0018), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00efngrid","family":"Gonz\u00e0lez-Casacuberta","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Ormazabal","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"},{"name":"Department of Clinical Biochemistry, Institut de Recerca de Sant Joan de Deu, Esplugues de Llobregat, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanza","family":"Mor\u00e9n","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Tolosa","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS, Institut de Neuroci\u00e8ncies, UB, 08036 Barcelona, Spain"},{"name":"Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06\/05\/0018), 28029 Madrid, Spain"},{"name":"Parkinson Disease and Movement Disorders Unit, Neurology Service, HCB, IDIBAPS, UB, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Fucho","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB), Consejo Superior Investigaciones 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de Sant Joan de Deu, Esplugues de Llobregat, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Valldeoriola","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS, Institut de Neuroci\u00e8ncies, UB, 08036 Barcelona, Spain"},{"name":"Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06\/05\/0018), 28029 Madrid, Spain"},{"name":"Parkinson Disease and Movement Disorders Unit, Neurology Service, HCB, IDIBAPS, UB, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"de la Torre-Lara","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS, Institut de Neuroci\u00e8ncies, UB, 08036 Barcelona, Spain"},{"name":"Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06\/05\/0018), 28029 Madrid, Spain"},{"name":"Parkinson Disease and Movement Disorders Unit, Neurology Service, HCB, IDIBAPS, UB, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Tob\u00edas","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), 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Josep","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garc\u00eda-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB), Consejo Superior Investigaciones Cient\u00edficas (CSIC), 08001 Barcelona, Spain"},{"name":"Liver Unit-HCB, IDIBAPS, 08036 Barcelona, Spain"},{"name":"USC Research Centre for ALPD, Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Carlos","family":"Fernandez-Checa","sequence":"additional","affiliation":[{"name":"Department of Cell Death and Proliferation, Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB), Consejo Superior Investigaciones Cient\u00edficas (CSIC), 08001 Barcelona, Spain"},{"name":"Liver Unit-HCB, IDIBAPS, 08036 Barcelona, Spain"},{"name":"USC Research Centre for ALPD, Keck School of Medicine, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS, Institut de Neuroci\u00e8ncies, UB, 08036 Barcelona, Spain"},{"name":"Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06\/05\/0018), 28029 Madrid, Spain"},{"name":"Parkinson Disease and Movement Disorders Unit, 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and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"},{"name":"Department of Clinical Biochemistry, Institut de Recerca de Sant Joan de Deu, Esplugues de Llobregat, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Fern\u00e1ndez-Santiago","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS, Institut de Neuroci\u00e8ncies, UB, 08036 Barcelona, Spain"},{"name":"Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06\/05\/0018), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-9933","authenticated-orcid":false,"given":"Gl\u00f2ria","family":"Garrabou","sequence":"additional","affiliation":[{"name":"Laboratory of Muscle Research and Mitochondrial Function, Department of Internal Medicine-Hospital Cl\u00ednic of Barcelona (HCB), Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science, University of Barcelona (UB), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red (CIBER) de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"ref_1","first-page":"e9853","article-title":"Diabetes Mellitus and Parkinson\u2019s Disease: Shared Pathophysiological Links and Possible Therapeutic 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