HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97162-1 |
| _version_ | 1818993463204511744 |
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| author | Cécile A. Ferré Anne Thouard Alexandre Bétourné Anne-Louise Le Dorze Pascale Belenguer Marie-Christine Miquel Jean-Michel Peyrin Daniel Gonzalez-Dunia Marion Szelechowski |
| author_facet | Cécile A. Ferré Anne Thouard Alexandre Bétourné Anne-Louise Le Dorze Pascale Belenguer Marie-Christine Miquel Jean-Michel Peyrin Daniel Gonzalez-Dunia Marion Szelechowski |
| author_sort | Cécile A. Ferré |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T20:42:27Z |
| format | Article |
| id | doaj.art-b237ff1101164e3aab9e0784ffce70d4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:42:27Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b237ff1101164e3aab9e0784ffce70d42022-12-21T19:27:06ZengNature PortfolioScientific Reports2045-23222021-09-0111111210.1038/s41598-021-97162-1HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neuronsCécile A. Ferré0Anne Thouard1Alexandre Bétourné2Anne-Louise Le Dorze3Pascale Belenguer4Marie-Christine Miquel5Jean-Michel Peyrin6Daniel Gonzalez-Dunia7Marion Szelechowski8Toulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPSToulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPSToulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPSToulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPSCentre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPSCentre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPSSorbonne Universités, Faculté des Sciences et Technologie, CNRS UMR 8246, INSERM U1130, Neurosciences Paris Seine, Institut de Biologie Paris SeineToulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPSToulouse Institute for Infectious and Inflamatory Diseases (Infinity), Université Toulouse, CNRS, Inserm, UPSAbstract 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.https://doi.org/10.1038/s41598-021-97162-1 |
| spellingShingle | Cécile A. Ferré Anne Thouard Alexandre Bétourné Anne-Louise Le Dorze Pascale Belenguer Marie-Christine Miquel Jean-Michel Peyrin Daniel Gonzalez-Dunia Marion Szelechowski HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons Scientific Reports |
| title | HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons |
| title_full | HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons |
| title_fullStr | HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons |
| title_full_unstemmed | HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons |
| title_short | HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons |
| title_sort | hspa9 mortalin mediates axo protection and modulates mitochondrial dynamics in neurons |
| url | https://doi.org/10.1038/s41598-021-97162-1 |
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