Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome

19 p.-2 fig.-1 tab.

Detalhes bibliográficos
Autores: Ugalde, Cristina, Hinttala, R., Timal, Sharita, Smeets, Roel, Rodenburg, Richard J., Uusimaa, J., van den Heuvel, Lambert P., Nijtmans, Leo G., Majamaa, Kari, Smeitink, Jan A.
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2007
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/374756
Acesso em linha:http://hdl.handle.net/10261/374756
Access Level:acceso abierto
Palavra-chave:NADH ubiquinone oxidorreductase deficiency
Assembly
mtDNA
Mitochondrial disorders
Leigh Syndrome
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spelling Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh SyndromeRunning title: Mutated ND2 in Leigh SyndromeUgalde, CristinaHinttala, R.Timal, SharitaSmeets, RoelRodenburg, Richard J.Uusimaa, J.van den Heuvel, Lambert P.Nijtmans, Leo G.Majamaa, KariSmeitink, Jan A.NADH ubiquinone oxidorreductase deficiencyAssemblymtDNAMitochondrial disordersLeigh Syndrome19 p.-2 fig.-1 tab.We describe a novel mitochondrial ND2 mutation (T4681C) in a patient presenting with Leigh Syndrome. Biochemical analyses revealed a low isolated complex I activity in patient's fibroblasts, blood and skeletal muscle. Mutant transmitochondrial cybrid clones retained the specific complex I defect, demonstrating the mitochondrial genetic origin of the disease. The mutation leads to a L71P substitution at an evolutionary conserved amino acid stretch. By two-dimensional blue native electrophoresis (2D-BN-SDS-PAGE), decreased complex I levels were observed together with an accumulation of specific assembly intermediates, suggesting that the mutation disturbs the complex I assembly pathway.This work was supported by “Het Prinses Beatrix Fonds” to J.S. and L.v.d.H. (Grant No. 02-0104) and by grants from the Medical Research Council of the Academy of Finland, the Sigrid Juselius Foundation and Finnish Neurological Foundation to K.M., The Arvo and Lea Ylppö Foundation and the Foundation for Pediatric Research to J.U. and The Alma and K.A. Snellman Foundation, Oulu, Finland and The Paivikki and Sakari Sohlberg Foundation to R.H. Part of this work was supported by the European Community’s sixth Framework Programme for Research, contract number LSHM-CT-2004-503116. The Netherlands Organization for Scientific Research supported L.N. with a “Vernieuwingsimpuls” grant. C.U. is recipient of a research contract from Instituto de Salud Carlos III (ISC III CP04/00011).Peer reviewedElsevierPrincess Beatrix Muscle FundAcademy of FinlandSigrid Juselius FoundationFinnish Brain FoundationArvo and Lea Ylppö FoundationFoundation for Pediatric Research (Finland)Alma and K. A. Snellman FoundationPäivikki and Sakari Sohlberg FoundationEuropean CommissionNetherlands Organization for Scientific ResearchInstituto de Salud Carlos IIIUgalde, Cristina [0000-0002-9742-1877]Hinttala, R. [0000-0002-7642-4008]Rodenburg, Richard J. [0000-0001-5227-3527]Majamaa, Kari [0000-0002-9070-3791]202420242007info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/374756reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1016/j.ymgme.2006.08.003Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3747562026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
Running title: Mutated ND2 in Leigh Syndrome
title Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
spellingShingle Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
Ugalde, Cristina
NADH ubiquinone oxidorreductase deficiency
Assembly
mtDNA
Mitochondrial disorders
Leigh Syndrome
title_short Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
title_full Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
title_fullStr Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
title_full_unstemmed Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
title_sort Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome
dc.creator.none.fl_str_mv Ugalde, Cristina
Hinttala, R.
Timal, Sharita
Smeets, Roel
Rodenburg, Richard J.
Uusimaa, J.
van den Heuvel, Lambert P.
Nijtmans, Leo G.
Majamaa, Kari
Smeitink, Jan A.
author Ugalde, Cristina
author_facet Ugalde, Cristina
Hinttala, R.
Timal, Sharita
Smeets, Roel
Rodenburg, Richard J.
Uusimaa, J.
van den Heuvel, Lambert P.
Nijtmans, Leo G.
Majamaa, Kari
Smeitink, Jan A.
author_role author
author2 Hinttala, R.
Timal, Sharita
Smeets, Roel
Rodenburg, Richard J.
Uusimaa, J.
van den Heuvel, Lambert P.
Nijtmans, Leo G.
Majamaa, Kari
Smeitink, Jan A.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Princess Beatrix Muscle Fund
Academy of Finland
Sigrid Juselius Foundation
Finnish Brain Foundation
Arvo and Lea Ylppö Foundation
Foundation for Pediatric Research (Finland)
Alma and K. A. Snellman Foundation
Päivikki and Sakari Sohlberg Foundation
European Commission
Netherlands Organization for Scientific Research
Instituto de Salud Carlos III
Ugalde, Cristina [0000-0002-9742-1877]
Hinttala, R. [0000-0002-7642-4008]
Rodenburg, Richard J. [0000-0001-5227-3527]
Majamaa, Kari [0000-0002-9070-3791]
dc.subject.none.fl_str_mv NADH ubiquinone oxidorreductase deficiency
Assembly
mtDNA
Mitochondrial disorders
Leigh Syndrome
topic NADH ubiquinone oxidorreductase deficiency
Assembly
mtDNA
Mitochondrial disorders
Leigh Syndrome
description 19 p.-2 fig.-1 tab.
publishDate 2007
dc.date.none.fl_str_mv 2007
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/10261/374756
url http://hdl.handle.net/10261/374756
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1016/j.ymgme.2006.08.003
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
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score 15,811543

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