Academic Journal
Mitochondrial respiratory chain disorganization in Parkinson’s disease-relevant PINK1 and DJ1 mutants
| العنوان: | Mitochondrial respiratory chain disorganization in Parkinson’s disease-relevant PINK1 and DJ1 mutants |
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| المؤلفون: | López-Fabuel, Irene, Martín-Martín, Lucía, Resch-Beusher, Mónica, Azkona Mendoza, Garikoitz, Sánchez Pernaute, Rosario, Bolaños Hernández, Juan Pedro |
| المساهمون: | European Commission |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2017 |
| المجموعة: | ADDI: Repositorio Institucional de la Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU - Basque Country University) |
| مصطلحات موضوعية: | complexes, DJ1, human, mouse, neurons, Parkinson's disease, mitochondria |
| الوصف: | Brain mitochondrial complex I (CI) damage is associated with the loss of the dopaminergic neurons of the Substantia Nigra in Parkinson's Disease (PD) patients. However, whether CI inhibition is associated with any alteration of the mitochondrial respiratory chain (MRC) organization in PD patients is unknown. To address this issue, here we analyzed the MRC by blue native gel electrophoresis (BNGE) followed by western blotting, in mitochondria purified from fibroblasts of patients harboring PD-relevant Pink1 mutations. We found a decrease in free CI, and in free versus supercomplexes (SCs)-assembled CI in PD; however, free complex III (CIII) was only modestly affected, whereas its free versus SCs-assembled forms decreased. Interestingly, complex IV (CIV) was considerably lost in the PD samples. These results were largely confirmed in mitochondria isolated from cultured neurons from Pink1-/- mice, and in cultured neurons and forebrain samples from the PD-related Dj1-/- mice. Thus, besides CI damage, the MRC undergoes a profound structural remodeling in PD likely responsible for the energetic inefficiency and mitochondrial reactive oxygen species (mROS) over-production observed in this disease. ; J.P.B. is funded by MINECO (SAF2016-78114-R; RTC-2015-3237-1), CIBERFES (CB16/10/00282), E.U. SP3-People-MC-ITN programme (608381), EU BATCure grant (666918) and FEDER (European regional development fund). R.S.P. is funded by the Joint Program in Neurodegenerative Diseases (DAMNDPATHS). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0197-0186 1872-9754 |
| Relation: | info:eu-repo/grantAgreement/MINECO/SAF2016-78114-R; info:eu-repo/grantAgreement/MINECO/RTC-2015-3237-1; info:eu-repo/grantAgreement/EC/FP7/08381; https://www.sciencedirect.com/science/article/pii/S0197018617300554; Neurochemistry International 109 : 101-105 (2017); http://hdl.handle.net/10810/65182; /10.1016/j.neuint.2017.03.023 |
| الاتاحة: | http://hdl.handle.net/10810/65182 |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; © 2017 Elsevier under CC BY-NC-ND license |
| رقم الانضمام: | edsbas.AFC162C7 |
| قاعدة البيانات: | BASE |
| تدمد: | 01970186 18729754 |
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