Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease

41 p.-5 fig.-2 tab.

Bibliographic Details
Authors: Pello, Rosa, Martín, Miguel Ángel, Carelli, Valerio, Nijtmans, Leo G., Achilli, Alessandro, Pala, Maria, Torroni, Antonio, Gómez-Durán, Aurora, Ruiz-Pesini, Eduardo, Martinuzzi, Andrea, Smeitink, Jan A., Arenas, Joaquín, Ugalde, Cristina
Format: article
Status:Versión aceptada para publicación
Publication Date:2008
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/369225
Online Access:http://hdl.handle.net/10261/369225
Access Level:Open access
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spelling Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial diseasePello, RosaMartín, Miguel ÁngelCarelli, ValerioNijtmans, Leo G.Achilli, AlessandroPala, MariaTorroni, AntonioGómez-Durán, AuroraRuiz-Pesini, EduardoMartinuzzi, AndreaSmeitink, Jan A.Arenas, JoaquínUgalde, Cristina41 p.-5 fig.-2 tab.Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disorder, is mostly due to three mitochondrial DNA (mtDNA) mutations in respiratory chain complex I subunit genes: 3460/ND1, 11778/ND4 and 14484/ND6. Despite considerable clinical evidences, a genetic modifying role of the mtDNA haplogroup background in the clinical expression of LHON remains experimentally unproven. We investigated the effect of mtDNA haplogroups on the assembly of oxidative phosphorylation (OXPHOS) complexes in transmitochondrial hybrids (cybrids) harboring the three common LHON mutations. The steady-state levels of respiratory chain complexes appeared normal in mutant cybrids. However, an accumulation of low molecular weight subcomplexes suggested a complex I assembly/stability defect, which was further demonstrated by reversibly inhibiting mitochondrial protein translation with doxycycline. Our results showed differentially delayed assembly rates of respiratory chain complexes I, III and IV amongst mutants belonging to different mtDNA haplogroups, revealing that specific mtDNA polymorphisms may modify the pathogenic potential of LHON mutations by affecting the overall assembly kinetics of OXPHOS complexes.This study was partially supported by Fundación de Investigación Biomédica del Hospital Universitario 12 de Octubre/Agencia Pedro Laín Entralgo, and Instituto de Salud Carlos III (ISCIII) to C.U. (grant numbers 04/00011 and PI05-0379), by Fundación ARAID and ISCIII to E.R.P. (PI05-0647), by a Telethon-Italy grant (#GGP06233) to V.C., by Progetti Ricerca Interesse Nazionale 2007 (Italian Ministry of the University) to A.T., and by Fundación de Investigación Médica Mutua Madrileña to M.A.M. (2005-069).Peer reviewedOxford University PressInstituto de Salud Carlos IIIFundación Agencia Aragonesa para la Investigación y el DesarrolloTelethon ItaliaMinistero dell'Istruzione, dell'Università e della RicercaFundación Mutua MadrileñaFundación para la Investigación Biomédica del Hospital Universitario 12 de OctubreCarelli, Valerio [0000-0003-4923-6404]Achilli, Alessandro [0000-0001-6871-3451]Pala, Maria [0000-0001-9202-8331]Torroni, Antonio [0000-0002-4163-4478]Gómez-Durán, Aurora [0000-0002-5895-6860]Ruiz-Pesini, Eduardo [0000-0002-0269-7337]Martinuzzi, Andrea [0000-0002-0319-3579]Arenas, Joaquín [0000-0002-2877-5049]Ugalde, Cristina [0000-0002-9742-1877]202420242008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/369225reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1093/hmg/ddn303Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3692252026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
title Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
spellingShingle Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
Pello, Rosa
title_short Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
title_full Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
title_fullStr Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
title_full_unstemmed Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
title_sort Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease
dc.creator.none.fl_str_mv Pello, Rosa
Martín, Miguel Ángel
Carelli, Valerio
Nijtmans, Leo G.
Achilli, Alessandro
Pala, Maria
Torroni, Antonio
Gómez-Durán, Aurora
Ruiz-Pesini, Eduardo
Martinuzzi, Andrea
Smeitink, Jan A.
Arenas, Joaquín
Ugalde, Cristina
author Pello, Rosa
author_facet Pello, Rosa
Martín, Miguel Ángel
Carelli, Valerio
Nijtmans, Leo G.
Achilli, Alessandro
Pala, Maria
Torroni, Antonio
Gómez-Durán, Aurora
Ruiz-Pesini, Eduardo
Martinuzzi, Andrea
Smeitink, Jan A.
Arenas, Joaquín
Ugalde, Cristina
author_role author
author2 Martín, Miguel Ángel
Carelli, Valerio
Nijtmans, Leo G.
Achilli, Alessandro
Pala, Maria
Torroni, Antonio
Gómez-Durán, Aurora
Ruiz-Pesini, Eduardo
Martinuzzi, Andrea
Smeitink, Jan A.
Arenas, Joaquín
Ugalde, Cristina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Fundación Agencia Aragonesa para la Investigación y el Desarrollo
Telethon Italia
Ministero dell'Istruzione, dell'Università e della Ricerca
Fundación Mutua Madrileña
Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre
Carelli, Valerio [0000-0003-4923-6404]
Achilli, Alessandro [0000-0001-6871-3451]
Pala, Maria [0000-0001-9202-8331]
Torroni, Antonio [0000-0002-4163-4478]
Gómez-Durán, Aurora [0000-0002-5895-6860]
Ruiz-Pesini, Eduardo [0000-0002-0269-7337]
Martinuzzi, Andrea [0000-0002-0319-3579]
Arenas, Joaquín [0000-0002-2877-5049]
Ugalde, Cristina [0000-0002-9742-1877]
description 41 p.-5 fig.-2 tab.
publishDate 2008
dc.date.none.fl_str_mv 2008
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/369225
url http://hdl.handle.net/10261/369225
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1093/hmg/ddn303
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424488563605504
score 15,812429

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