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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Autores principales:	Cécile A. Ferré, Anne Thouard, Alexandre Bétourné, Anne-Louise Le Dorze, Pascale Belenguer, Marie-Christine Miquel, Jean-Michel Peyrin, Daniel Gonzalez-Dunia, Marion Szelechowski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b237ff1101164e3aab9e0784ffce70d4
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spelling	oai:doaj.org-article:b237ff1101164e3aab9e0784ffce70d42021-12-02T17:19:14ZHSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons10.1038/s41598-021-97162-12045-2322https://doaj.org/article/b237ff1101164e3aab9e0784ffce70d42021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97162-1https://doaj.org/toc/2045-2322Abstract 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.Cécile A. FerréAnne ThouardAlexandre BétournéAnne-Louise Le DorzePascale BelenguerMarie-Christine MiquelJean-Michel PeyrinDaniel Gonzalez-DuniaMarion SzelechowskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	hspa9/mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b237ff1101164e3aab9e0784ffce70d4
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HSPA9/Mortalin mediates axo-protection and modulates mitochondrial dynamics in neurons

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