Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.

Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specifi...

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Authors: Lechuga-Vieco, Ana V., Latorre-Pellicer, Ana, Johnston, Iain G, Prota, Gennaro, Gileadi, Uzi, Justo-Mendez, Raquel, Acin-Perez, Rebeca, Martínez-de-Mena, Raquel, Fernandez-Toro, Jose Maria, Jimenez-Blasco, Daniel, Mora, Alfonso, Nicolas-Avila, Jose A., Santiago, Demetrio J, Priori, Silvia G., Bolaños, Juan Pedro, Sabio, Guadalupe, Criado-Rodriguez, Luis M., Ruiz-Cabello, Jesus, Cerundolo, Vincenzo, Jones, Nick S, Enriquez, Jose Antonio
Format: article
Publication Date:2020
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/11255
Online Access:http://hdl.handle.net/20.500.12105/11255
Access Level:Open access
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spelling Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.Lechuga-Vieco, Ana V.Latorre-Pellicer, AnaJohnston, Iain GProta, GennaroGileadi, UziJusto-Mendez, RaquelAcin-Perez, RebecaMartínez-de-Mena, RaquelFernandez-Toro, Jose MariaJimenez-Blasco, DanielMora, AlfonsoNicolas-Avila, Jose A.Santiago, Demetrio JPriori, Silvia G.Bolaños, Juan PedroSabio, GuadalupeCriado-Rodriguez, Luis M.Ruiz-Cabello, JesusCerundolo, VincenzoJones, Nick SEnriquez, Jose AntonioHeteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specific mtDNA segregation pattern, with few tissues that do not show segregation. The driving force for this dynamic complex pattern has remained unexplained for decades, challenging our understanding of this fundamental biological problem and hindering clinical planning for inherited diseases. Here, we demonstrate that the nonrandom mtDNA segregation is an intracellular process based on organelle selection. This cell type-specific decision arises jointly from the impact of mtDNA haplotypes on the oxidative phosphorylation (OXPHOS) system and the cell metabolic requirements and is strongly sensitive to the nuclear context and to environmental cues.American Association for the Advancement of Science (AAAS)Ministerio de Economía y Competitividad (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Comunidad de Madrid (España)Unión Europea. Comisión EuropeaCentro de Investigación Biomedica en Red - CIBERMedical Research Council (Reino Unido)Cancer Research UK (Reino Unido)Unión Europea. Comisión Europea. European Research Council (ERC)Fundación ProCNICFundación BBVA20202020-10-2820202020-07-0120202020-07-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/20.500.12105/11255reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SEV-2015-0505 Not availableES SAF2015-65633-R Not availableES SAF2016-78114-R Not availableES SAF2017-84494-C2-1-R Not availableES SAF2016-79126-R Not availableEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 666918European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 805046ES MDM-2017-0720 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/112552026-06-12T12:43:37Z
dc.title.none.fl_str_mv Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
title Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
spellingShingle Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
Lechuga-Vieco, Ana V.
title_short Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
title_full Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
title_fullStr Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
title_full_unstemmed Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
title_sort Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics.
dc.creator.none.fl_str_mv Lechuga-Vieco, Ana V.
Latorre-Pellicer, Ana
Johnston, Iain G
Prota, Gennaro
Gileadi, Uzi
Justo-Mendez, Raquel
Acin-Perez, Rebeca
Martínez-de-Mena, Raquel
Fernandez-Toro, Jose Maria
Jimenez-Blasco, Daniel
Mora, Alfonso
Nicolas-Avila, Jose A.
Santiago, Demetrio J
Priori, Silvia G.
Bolaños, Juan Pedro
Sabio, Guadalupe
Criado-Rodriguez, Luis M.
Ruiz-Cabello, Jesus
Cerundolo, Vincenzo
Jones, Nick S
Enriquez, Jose Antonio
author Lechuga-Vieco, Ana V.
author_facet Lechuga-Vieco, Ana V.
Latorre-Pellicer, Ana
Johnston, Iain G
Prota, Gennaro
Gileadi, Uzi
Justo-Mendez, Raquel
Acin-Perez, Rebeca
Martínez-de-Mena, Raquel
Fernandez-Toro, Jose Maria
Jimenez-Blasco, Daniel
Mora, Alfonso
Nicolas-Avila, Jose A.
Santiago, Demetrio J
Priori, Silvia G.
Bolaños, Juan Pedro
Sabio, Guadalupe
Criado-Rodriguez, Luis M.
Ruiz-Cabello, Jesus
Cerundolo, Vincenzo
Jones, Nick S
Enriquez, Jose Antonio
author_role author
author2 Latorre-Pellicer, Ana
Johnston, Iain G
Prota, Gennaro
Gileadi, Uzi
Justo-Mendez, Raquel
Acin-Perez, Rebeca
Martínez-de-Mena, Raquel
Fernandez-Toro, Jose Maria
Jimenez-Blasco, Daniel
Mora, Alfonso
Nicolas-Avila, Jose A.
Santiago, Demetrio J
Priori, Silvia G.
Bolaños, Juan Pedro
Sabio, Guadalupe
Criado-Rodriguez, Luis M.
Ruiz-Cabello, Jesus
Cerundolo, Vincenzo
Jones, Nick S
Enriquez, Jose Antonio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Comunidad de Madrid (España)
Unión Europea. Comisión Europea
Centro de Investigación Biomedica en Red - CIBER
Medical Research Council (Reino Unido)
Cancer Research UK (Reino Unido)
Unión Europea. Comisión Europea. European Research Council (ERC)
Fundación ProCNIC
Fundación BBVA
description Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specific mtDNA segregation pattern, with few tissues that do not show segregation. The driving force for this dynamic complex pattern has remained unexplained for decades, challenging our understanding of this fundamental biological problem and hindering clinical planning for inherited diseases. Here, we demonstrate that the nonrandom mtDNA segregation is an intracellular process based on organelle selection. This cell type-specific decision arises jointly from the impact of mtDNA haplotypes on the oxidative phosphorylation (OXPHOS) system and the cell metabolic requirements and is strongly sensitive to the nuclear context and to environmental cues.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-10-28
2020
2020-07-01
2020
2020-07-01
dc.type.none.fl_str_mv journal 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 http://hdl.handle.net/20.500.12105/11255
url http://hdl.handle.net/20.500.12105/11255
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES SEV-2015-0505 Not available
ES SAF2015-65633-R Not available
ES SAF2016-78114-R Not available
ES SAF2017-84494-C2-1-R Not available
ES SAF2016-79126-R Not available
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 666918
European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 805046
ES MDM-2017-0720 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/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
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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