Ndufs4 knockout mouse models of Leigh syndrome

Mitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial disease...

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Autores: van de Wal, Melissa A. E., Adjobo-Hermans, Merel J. W.|||0000-0002-5947-2876, Keijer, Jaap|||0000-0002-9720-7491, Schirris, Tom J. J.|||0000-0002-7621-1010, Homberg, Judith R., Wieckowski, Mariusz R.|||0000-0003-0789-4521, Grefte, Sander|||0000-0002-8502-6298, van Schothorst, Evert M.|||0000-0002-3036-5903, van Karnebeek, Clara|||0000-0002-2648-8337, Quintana Romero, Albert|||0000-0003-1674-7160, Koopman, Werner J. H.|||0000-0002-3364-0069
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:258134
Acesso em linha:https://ddd.uab.cat/record/258134
https://dx.doi.org/urn:doi:10.1093/brain/awab426
Access Level:acceso abierto
Palavra-chave:Leigh syndrome
Mouse model
Pathomechanism
Intervention
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spelling Ndufs4 knockout mouse models of Leigh syndromepathophysiology and interventionvan de Wal, Melissa A. E.Adjobo-Hermans, Merel J. W.|||0000-0002-5947-2876Keijer, Jaap|||0000-0002-9720-7491Schirris, Tom J. J.|||0000-0002-7621-1010Homberg, Judith R.Wieckowski, Mariusz R.|||0000-0003-0789-4521Grefte, Sander|||0000-0002-8502-6298van Schothorst, Evert M.|||0000-0002-3036-5903van Karnebeek, Clara|||0000-0002-2648-8337Quintana Romero, Albert|||0000-0003-1674-7160Koopman, Werner J. H.|||0000-0002-3364-0069Leigh syndromeMouse modelPathomechanismInterventionMitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial diseases. With respect to the latter, mutations in subunit-encoding genes and assembly factors of the first OXPHOS complex (complex I) induce isolated complex I deficiency and Leigh syndrome. This syndrome is an early-onset, often fatal, encephalopathy with a variable clinical presentation and poor prognosis due to the lack of effective intervention strategies. Mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce 'mitochondrial complex I deficiency, nuclear type 1' (MC1DN1) and Leigh syndrome in paediatric patients. A variety of (tissue-specific) Ndufs4 knockout mouse models were developed to study the Leigh syndrome pathomechanism and intervention testing. Here, we review and discuss the role of complex I and NDUFS4 mutations in human mitochondrial disease, and review how the analysis of Ndufs4 knockout mouse models has generated new insights into the MC1ND1/Leigh syndrome pathomechanism and its therapeutic targeting. The NDUFS4 gene encodes an accessory subunit of OXPHOS complex I and its mutation causes mitochondrial disease in children. Van de Wal et al. review how Ndufs4 knockout mouse models have provided new insights into the disease pathomechanism and potential intervention strategies for these disorders. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/258134https://dx.doi.org/urn:doi:10.1093/brain/awab426reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 638106Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-88108-R"la Caixa" Foundation https://doi.org/10.13039/100010434 LCF/PR/HR20/52400018open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2581342026-06-06T12:50:31Z
dc.title.none.fl_str_mv Ndufs4 knockout mouse models of Leigh syndrome
pathophysiology and intervention
title Ndufs4 knockout mouse models of Leigh syndrome
spellingShingle Ndufs4 knockout mouse models of Leigh syndrome
van de Wal, Melissa A. E.
Leigh syndrome
Mouse model
Pathomechanism
Intervention
title_short Ndufs4 knockout mouse models of Leigh syndrome
title_full Ndufs4 knockout mouse models of Leigh syndrome
title_fullStr Ndufs4 knockout mouse models of Leigh syndrome
title_full_unstemmed Ndufs4 knockout mouse models of Leigh syndrome
title_sort Ndufs4 knockout mouse models of Leigh syndrome
dc.creator.none.fl_str_mv van de Wal, Melissa A. E.
Adjobo-Hermans, Merel J. W.|||0000-0002-5947-2876
Keijer, Jaap|||0000-0002-9720-7491
Schirris, Tom J. J.|||0000-0002-7621-1010
Homberg, Judith R.
Wieckowski, Mariusz R.|||0000-0003-0789-4521
Grefte, Sander|||0000-0002-8502-6298
van Schothorst, Evert M.|||0000-0002-3036-5903
van Karnebeek, Clara|||0000-0002-2648-8337
Quintana Romero, Albert|||0000-0003-1674-7160
Koopman, Werner J. H.|||0000-0002-3364-0069
author van de Wal, Melissa A. E.
author_facet van de Wal, Melissa A. E.
Adjobo-Hermans, Merel J. W.|||0000-0002-5947-2876
Keijer, Jaap|||0000-0002-9720-7491
Schirris, Tom J. J.|||0000-0002-7621-1010
Homberg, Judith R.
Wieckowski, Mariusz R.|||0000-0003-0789-4521
Grefte, Sander|||0000-0002-8502-6298
van Schothorst, Evert M.|||0000-0002-3036-5903
van Karnebeek, Clara|||0000-0002-2648-8337
Quintana Romero, Albert|||0000-0003-1674-7160
Koopman, Werner J. H.|||0000-0002-3364-0069
author_role author
author2 Adjobo-Hermans, Merel J. W.|||0000-0002-5947-2876
Keijer, Jaap|||0000-0002-9720-7491
Schirris, Tom J. J.|||0000-0002-7621-1010
Homberg, Judith R.
Wieckowski, Mariusz R.|||0000-0003-0789-4521
Grefte, Sander|||0000-0002-8502-6298
van Schothorst, Evert M.|||0000-0002-3036-5903
van Karnebeek, Clara|||0000-0002-2648-8337
Quintana Romero, Albert|||0000-0003-1674-7160
Koopman, Werner J. H.|||0000-0002-3364-0069
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leigh syndrome
Mouse model
Pathomechanism
Intervention
topic Leigh syndrome
Mouse model
Pathomechanism
Intervention
description Mitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial diseases. With respect to the latter, mutations in subunit-encoding genes and assembly factors of the first OXPHOS complex (complex I) induce isolated complex I deficiency and Leigh syndrome. This syndrome is an early-onset, often fatal, encephalopathy with a variable clinical presentation and poor prognosis due to the lack of effective intervention strategies. Mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce 'mitochondrial complex I deficiency, nuclear type 1' (MC1DN1) and Leigh syndrome in paediatric patients. A variety of (tissue-specific) Ndufs4 knockout mouse models were developed to study the Leigh syndrome pathomechanism and intervention testing. Here, we review and discuss the role of complex I and NDUFS4 mutations in human mitochondrial disease, and review how the analysis of Ndufs4 knockout mouse models has generated new insights into the MC1ND1/Leigh syndrome pathomechanism and its therapeutic targeting. The NDUFS4 gene encodes an accessory subunit of OXPHOS complex I and its mutation causes mitochondrial disease in children. Van de Wal et al. review how Ndufs4 knockout mouse models have provided new insights into the disease pathomechanism and potential intervention strategies for these disorders.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
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 https://ddd.uab.cat/record/258134
https://dx.doi.org/urn:doi:10.1093/brain/awab426
url https://ddd.uab.cat/record/258134
https://dx.doi.org/urn:doi:10.1093/brain/awab426
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission https://doi.org/10.13039/501100000780 638106
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-88108-R
"la Caixa" Foundation https://doi.org/10.13039/100010434 LCF/PR/HR20/52400018
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
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
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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