Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism

Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by recessive mutations in the frataxin gene that lead to a deficiency of the mitochondrial frataxin (FXN) protein. Alternative forms of frataxin have been described, with different cellular localization and tissue distribution, includi...

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Detalhes bibliográficos
Autores: Agrò, Mauro, Díaz Nido, Javier
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/708768
Acesso em linha:http://hdl.handle.net/10486/708768
https://dx.doi.org/10.3390/ijms21218251
Access Level:acceso abierto
Palavra-chave:Frataxin
Iron Binding Protein
Isoprotein
Mitochondrion
Biología y Biomedicina / Biología
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repository_id_str
spelling Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolismAgrò, MauroDíaz Nido, JavierFrataxinIron Binding ProteinIsoproteinMitochondrionBiología y Biomedicina / BiologíaFriedreich’s ataxia (FRDA) is a neurodegenerative disease caused by recessive mutations in the frataxin gene that lead to a deficiency of the mitochondrial frataxin (FXN) protein. Alternative forms of frataxin have been described, with different cellular localization and tissue distribution, including a cerebellum-specific cytosolic isoform called FXN II. Here, we explored the functional roles of FXN II in comparison to the mitochondrial FXN I isoform, highlighting the existence of potential cross-talk between cellular compartments. To achieve this, we transduced two human cell lines of patient and healthy subjects with lentiviral vectors overexpressing the mitochondrial or the cytosolic FXN isoforms and studied their effect on the mitochondrial network and metabolism. We confirmed the cytosolic localization of FXN isoform II in our in vitro models. Interestingly, both cytosolic and mitochondrial isoforms have an effect on mitochondrial dynamics, affecting different parameters. Accordingly, increases of mitochondrial respiration were detected after transduction with FXN I or FXN II in both cellular models. Together, these results point to the existence of a potential cross-talk mechanism between the cytosol and mitochondria, mediated by FXN isoforms. A more thorough knowledge of the mechanisms of action behind the extra-mitochondrial FXN II isoform could prove useful in unraveling FRDA physiopathologyPID2019-111338RB-100, Comunidad de Madrid (NEUROMETAB-CM, B2017/BMD-3700)MDPIDepartamento de Biología MolecularFacultad de Ciencias20202020-11-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/708768https://dx.doi.org/10.3390/ijms21218251reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7087682026-06-23T12:46:27Z
dc.title.none.fl_str_mv Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
title Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
spellingShingle Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
Agrò, Mauro
Frataxin
Iron Binding Protein
Isoprotein
Mitochondrion
Biología y Biomedicina / Biología
title_short Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
title_full Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
title_fullStr Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
title_full_unstemmed Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
title_sort Effect of mitochondrial and cytosolic fxn isoform expression on mitochondrial dynamics and metabolism
dc.creator.none.fl_str_mv Agrò, Mauro
Díaz Nido, Javier
author Agrò, Mauro
author_facet Agrò, Mauro
Díaz Nido, Javier
author_role author
author2 Díaz Nido, Javier
author2_role author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Frataxin
Iron Binding Protein
Isoprotein
Mitochondrion
Biología y Biomedicina / Biología
topic Frataxin
Iron Binding Protein
Isoprotein
Mitochondrion
Biología y Biomedicina / Biología
description Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by recessive mutations in the frataxin gene that lead to a deficiency of the mitochondrial frataxin (FXN) protein. Alternative forms of frataxin have been described, with different cellular localization and tissue distribution, including a cerebellum-specific cytosolic isoform called FXN II. Here, we explored the functional roles of FXN II in comparison to the mitochondrial FXN I isoform, highlighting the existence of potential cross-talk between cellular compartments. To achieve this, we transduced two human cell lines of patient and healthy subjects with lentiviral vectors overexpressing the mitochondrial or the cytosolic FXN isoforms and studied their effect on the mitochondrial network and metabolism. We confirmed the cytosolic localization of FXN isoform II in our in vitro models. Interestingly, both cytosolic and mitochondrial isoforms have an effect on mitochondrial dynamics, affecting different parameters. Accordingly, increases of mitochondrial respiration were detected after transduction with FXN I or FXN II in both cellular models. Together, these results point to the existence of a potential cross-talk mechanism between the cytosol and mitochondria, mediated by FXN isoforms. A more thorough knowledge of the mechanisms of action behind the extra-mitochondrial FXN II isoform could prove useful in unraveling FRDA physiopathology
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-11-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/708768
https://dx.doi.org/10.3390/ijms21218251
url http://hdl.handle.net/10486/708768
https://dx.doi.org/10.3390/ijms21218251
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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