دورية أكاديمية
HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons
| العنوان: | HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons |
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| المؤلفون: | Ferré, Cécile, Thouard, Anne, Bétourné, Alexandre, Le Dorze, Anne-Louise, Belenguer, Pascale, Miquel, Marie-Christine, Peyrin, Jean-Michel, Gonzalez-Dunia, Daniel, Szelechowski, Marion |
| المساهمون: | Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-12-EMMA-0016,X-protect,Propriétés neuroprotectrices de peptides dérivés de la protéine X du Bornavirus(2012), ANR-16-CE16-0013,MitoX,Analyse des mécanismes moléculaires et cellulaires des propriétés neuroprotectrices d'une protéine virale(2016) |
| المصدر: | ISSN: 2045-2322. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2021 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | MESH: Animals, MESH: Cerebral Cortex / drug effects, MESH: Rats, Sprague-Dawley, MESH: Rotenone / pharmacology, MESH: Cerebral Cortex / metabolism, MESH: HSP70 Heat-Shock Proteins / genetics, MESH: HSP70 Heat-Shock Proteins / metabolism, MESH: Mitochondrial Dynamics / drug effects, MESH: Mitochondrial Dynamics / physiology, MESH: Neurons / drug effects, MESH: Neurons / metabolism, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Mortalin is a mitochondrial chaperone protein involved in quality control of proteins imported into the mitochondrial matrix, which was recently described as a sensor of neuronal stress. Mortalin is down-regulated in neurons of patients with neurodegenerative diseases and levels of Mortalin expression are correlated with neuronal fate in animal models of Alzheimer's disease or cerebral ischemia. To date, however, the links between Mortalin levels, its impact on mitochondrial function and morphology and, ultimately, the initiation of neurodegeneration, are still unclear. In the present study, we used lentiviral vectors to over- or under-express Mortalin in primary neuronal cultures. We first analyzed the early events of neurodegeneration in the axonal compartment, using oriented neuronal cultures grown in microfluidic-based devices. We observed that Mortalin down-regulation induced mitochondrial fragmentation and axonal damage, whereas its over-expression conferred protection against axonal degeneration mediated by rotenone exposure. We next demonstrated that Mortalin levels modulated mitochondrial morphology by acting on DRP1 phosphorylation, thereby further illustrating the crucial implication of mitochondrial dynamics on neuronal fate in degenerative diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34489498; hal-03365325; https://hal.science/hal-03365325Test; https://hal.science/hal-03365325/documentTest; https://hal.science/hal-03365325/file/41598_2021_Article_97162.pdfTest; PUBMED: 34489498; PUBMEDCENTRAL: PMC8421332 |
| DOI: | 10.1038/s41598-021-97162-1 |
| الإتاحة: | https://doi.org/10.1038/s41598-021-97162-1Test https://hal.science/hal-03365325Test https://hal.science/hal-03365325/documentTest https://hal.science/hal-03365325/file/41598_2021_Article_97162.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.9D7CA50A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-021-97162-1 |
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