Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species

The apoptotic nuclease EndoG is involved in mitochondrial DNA replication. Previous results suggested that, in addition to regulate cardiomyocyte hypertrophy, EndoG could be involved in cell proliferation. Here, by using in vivo and cell culture models, we investigated the role of EndoG in cell prol...

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Autores: Blasco Angulo, Natividad, Beà Tàrrega, Aida, Barés Junqué, Gisel, Girón, Cristina, Navaridas Fernández de Bobadilla, Raúl, Irazoki, Andrea, López-Lluch, Guillermo, Zorzano, Antonio, Dolcet Roca, Xavier, Llovera i Tomàs, Marta, Sanchis, Daniel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/70681
Acceso en línea:https://doi.org/10.1016/j.redox.2020.101736
http://hdl.handle.net/10459.1/70681
Access Level:acceso abierto
Palabra clave:EndoG
Cell proliferation
Mitochondria
Reactive oxygen species
Cell signaling
Humanin
Romo1
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spelling Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen speciesBlasco Angulo, NatividadBeà Tàrrega, AidaBarés Junqué, GiselGirón, CristinaNavaridas Fernández de Bobadilla, RaúlIrazoki, AndreaLópez-Lluch, GuillermoZorzano, AntonioDolcet Roca, XavierLlovera i Tomàs, MartaSanchis, DanielEndoGCell proliferationMitochondriaReactive oxygen speciesCell signalingHumaninRomo1The apoptotic nuclease EndoG is involved in mitochondrial DNA replication. Previous results suggested that, in addition to regulate cardiomyocyte hypertrophy, EndoG could be involved in cell proliferation. Here, by using in vivo and cell culture models, we investigated the role of EndoG in cell proliferation. Genetic deletion of Endog both in vivo and in cultured cells or Endog silencing in vitro induced a defect in rodent and human cell proliferation with a tendency of cells to accumulate in the G1 phase of cell cycle and increased reactive oxygen species (ROS) production. The defect in cell proliferation occurred with a decrease in the activity of the AKT/PKB-GSK-3β-Cyclin D axis and was reversed by addition of ROS scavengers. EndoG deficiency did not affect the expression of ROS detoxifying enzymes, nor the expression of the electron transport chain complexes and oxygen consumption rate. Addition of the micropeptide Humanin to EndoG-deficient cells restored AKT phosphorylation and proliferation without lowering ROS levels. Thus, our results show that EndoG is important for cell proliferation through the control of ROS and that Humanin can restore cell division in EndoG-deficient cells and counteracts the effects of ROS on AKT phosphorylation.This research was funded by Ministerio de Ciencia e Innovación, Gobierno de España, grant numbers SAF2013-44942-R and PID2019-104509RB-I00 to D.S. and SAF2016-80157-R to X.D.; Fundació La Marató, Catalunya, grant number 20153810 to D.S.; AGAUR, Generalitat de Catalunya, Catalunya, grant number 2014-SGR-1609 to D.S. G.B. holds a contract from the University of Lleida; A.B. contract has been funded by Fundació La Marató TV3 and Diputació de Lleida/IRBLleida.Elsevier2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.1016/j.redox.2020.101736http://hdl.handle.net/10459.1/70681http://hdl.handle.net/10459.1/70681reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/MINECO//SAF2013-44942-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104509RB-I00info:eu-repo/grantAgreement/MINECO//SAF2016-80157-RReproducció del document publicat a: https://doi.org/10.1016/j.redox.2020.101736Redox Biology, 2020, vol. 37, p. 101736cc-by-nc-nd (c) Blasco Angulo, Natividad et al., 2020info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:recercat.cat:10459.1/706812026-05-29T05:05:01Z
dc.title.none.fl_str_mv Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
title Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
spellingShingle Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
Blasco Angulo, Natividad
EndoG
Cell proliferation
Mitochondria
Reactive oxygen species
Cell signaling
Humanin
Romo1
title_short Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
title_full Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
title_fullStr Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
title_full_unstemmed Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
title_sort Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species
dc.creator.none.fl_str_mv Blasco Angulo, Natividad
Beà Tàrrega, Aida
Barés Junqué, Gisel
Girón, Cristina
Navaridas Fernández de Bobadilla, Raúl
Irazoki, Andrea
López-Lluch, Guillermo
Zorzano, Antonio
Dolcet Roca, Xavier
Llovera i Tomàs, Marta
Sanchis, Daniel
author Blasco Angulo, Natividad
author_facet Blasco Angulo, Natividad
Beà Tàrrega, Aida
Barés Junqué, Gisel
Girón, Cristina
Navaridas Fernández de Bobadilla, Raúl
Irazoki, Andrea
López-Lluch, Guillermo
Zorzano, Antonio
Dolcet Roca, Xavier
Llovera i Tomàs, Marta
Sanchis, Daniel
author_role author
author2 Beà Tàrrega, Aida
Barés Junqué, Gisel
Girón, Cristina
Navaridas Fernández de Bobadilla, Raúl
Irazoki, Andrea
López-Lluch, Guillermo
Zorzano, Antonio
Dolcet Roca, Xavier
Llovera i Tomàs, Marta
Sanchis, Daniel
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EndoG
Cell proliferation
Mitochondria
Reactive oxygen species
Cell signaling
Humanin
Romo1
topic EndoG
Cell proliferation
Mitochondria
Reactive oxygen species
Cell signaling
Humanin
Romo1
description The apoptotic nuclease EndoG is involved in mitochondrial DNA replication. Previous results suggested that, in addition to regulate cardiomyocyte hypertrophy, EndoG could be involved in cell proliferation. Here, by using in vivo and cell culture models, we investigated the role of EndoG in cell proliferation. Genetic deletion of Endog both in vivo and in cultured cells or Endog silencing in vitro induced a defect in rodent and human cell proliferation with a tendency of cells to accumulate in the G1 phase of cell cycle and increased reactive oxygen species (ROS) production. The defect in cell proliferation occurred with a decrease in the activity of the AKT/PKB-GSK-3β-Cyclin D axis and was reversed by addition of ROS scavengers. EndoG deficiency did not affect the expression of ROS detoxifying enzymes, nor the expression of the electron transport chain complexes and oxygen consumption rate. Addition of the micropeptide Humanin to EndoG-deficient cells restored AKT phosphorylation and proliferation without lowering ROS levels. Thus, our results show that EndoG is important for cell proliferation through the control of ROS and that Humanin can restore cell division in EndoG-deficient cells and counteracts the effects of ROS on AKT phosphorylation.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.redox.2020.101736
http://hdl.handle.net/10459.1/70681
http://hdl.handle.net/10459.1/70681
url https://doi.org/10.1016/j.redox.2020.101736
http://hdl.handle.net/10459.1/70681
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//SAF2013-44942-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104509RB-I00
info:eu-repo/grantAgreement/MINECO//SAF2016-80157-R
Reproducció del document publicat a: https://doi.org/10.1016/j.redox.2020.101736
Redox Biology, 2020, vol. 37, p. 101736
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Blasco Angulo, Natividad et al., 2020
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd (c) Blasco Angulo, Natividad et al., 2020
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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