Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity

The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first exampl...

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Detalles Bibliográficos
Autores: Cruz-Bermúdez, Alberto, Vicente-Blanco, Ramiro J., Hernández-Sierra, Rosana, Montero, Mayte, Alvarez, Javier, González Manrique, Mar, Blázquez, Alberto, Martín, Miguel Ángel, Ayuso García, María del Carmen Tomasa, Garesse Alarcón, Rafael, Fernández Moreno, Miguel Ángel
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/676699
Acceso en línea:http://hdl.handle.net/10486/676699
https://dx.doi.org/10.1371/journal.pone.0146816
Access Level:acceso abierto
Palabra clave:Mitochondrial
Mutations
Characterization
Synergistic effect
Medicina
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spelling Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activityCruz-Bermúdez, AlbertoVicente-Blanco, Ramiro J.Hernández-Sierra, RosanaMontero, MayteAlvarez, JavierGonzález Manrique, MarBlázquez, AlbertoMartín, Miguel ÁngelAyuso García, María del Carmen TomasaGaresse Alarcón, RafaelFernández Moreno, Miguel ÁngelMitochondrialMutationsCharacterizationSynergistic effectMedicinaThe presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutationsThis work was supported by Instituto de Salud Carlos III, http://www.isciii.es/, PI 04/1001 to M. A.F.M.; Instituto de Salud Carlos III, http://www.isciii. es/, PI12/01683 to M.A.M.; Instituto de Salud Carlos III, http://www.isciii.es/, PI13/00556 to R.G.; Comunidad Autónoma de Madrid, http://www.madrid. org/cs/Satellite?pagename=ComunidadMadrid/ Home, S2010/BMD-2402 to R.G.; Fundación Mutua Madrileña, http://www.fundacionmutua.es/, 10.04.02.0064 to M.A.F.M.; The Spanish Ministry of Economy and Competitiveness, http://www.mineco. gob.es/, BFU2011-25763 to J.A.; FEDER funds from the E.U. to R.G., http://ec.europa.eu/regional_policy/ es/funding/erdfPublic Library of ScienceDepartamento de BioquímicaFacultad de Medicina20162016-01-19research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/676699https://dx.doi.org/10.1371/journal.pone.0146816reponame: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:10486/6766992026-06-23T12:46:27Z
dc.title.none.fl_str_mv Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
title Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
spellingShingle Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
Cruz-Bermúdez, Alberto
Mitochondrial
Mutations
Characterization
Synergistic effect
Medicina
title_short Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
title_full Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
title_fullStr Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
title_full_unstemmed Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
title_sort Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity
dc.creator.none.fl_str_mv Cruz-Bermúdez, Alberto
Vicente-Blanco, Ramiro J.
Hernández-Sierra, Rosana
Montero, Mayte
Alvarez, Javier
González Manrique, Mar
Blázquez, Alberto
Martín, Miguel Ángel
Ayuso García, María del Carmen Tomasa
Garesse Alarcón, Rafael
Fernández Moreno, Miguel Ángel
author Cruz-Bermúdez, Alberto
author_facet Cruz-Bermúdez, Alberto
Vicente-Blanco, Ramiro J.
Hernández-Sierra, Rosana
Montero, Mayte
Alvarez, Javier
González Manrique, Mar
Blázquez, Alberto
Martín, Miguel Ángel
Ayuso García, María del Carmen Tomasa
Garesse Alarcón, Rafael
Fernández Moreno, Miguel Ángel
author_role author
author2 Vicente-Blanco, Ramiro J.
Hernández-Sierra, Rosana
Montero, Mayte
Alvarez, Javier
González Manrique, Mar
Blázquez, Alberto
Martín, Miguel Ángel
Ayuso García, María del Carmen Tomasa
Garesse Alarcón, Rafael
Fernández Moreno, Miguel Ángel
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Bioquímica
Facultad de Medicina
dc.subject.none.fl_str_mv Mitochondrial
Mutations
Characterization
Synergistic effect
Medicina
topic Mitochondrial
Mutations
Characterization
Synergistic effect
Medicina
description The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-19
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/10486/676699
https://dx.doi.org/10.1371/journal.pone.0146816
url http://hdl.handle.net/10486/676699
https://dx.doi.org/10.1371/journal.pone.0146816
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 Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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