DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion

The early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been ide...

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Detalles Bibliográficos
Autores: Gallinat, A, Rakovic, A, Klein, C, Badimon, L
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p14874
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14874
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143379982&doi=10.1016%2fj.freeradbiomed.2022.10.315&partnerID=40&md5=b15934c34d5ef482f3bf893ed9ce98da
Access Level:acceso abierto
Palabra clave:DJ-1
PARK7
Ischemia
reperfusion
RNA-Binding
Mitochondria
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spelling DJ-1 regulates mitochondrial gene expression during ischemia and reperfusionGallinat, ARakovic, AKlein, CBadimon, LDJ-1PARK7IschemiareperfusionRNA-BindingMitochondriaThe early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been identified. However, no functional charac-terization has been provided to date. Here, we have investigated the DJ-1-interacting transcripts, as well as the role of DJ-1 RNA-binding activity during ischemia and reperfusion. Among the identified DJ-1-interacting transcripts, we have distinguished a significant enrichment of mRNAs encoding mitochondrial proteins. The effects of DJ-1 depletion on mitochondrial protein expression and mitochondrial morphology were investigated using a CRISPR/Cas9 generated DJ-1 knockout (DJ-1KO) cell model. DJ-1 depletion resulted in increased MTND2 protein expression in resting cells; however, after exposure to I/R, MTND2 levels were significantly reduced with respect to wild type cells. Increased mitochondrial fission was consistently found in DJ-1KO cells after I/R exposure. MTND2 transcript binding to DJ-1 was increased during ischemia. Our results indicate that the RNA -binding activity of DJ-1 shield mitochondrial transcripts from oxidative damage.ELSEVIER SCIENCE INC2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14874https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143379982&doi=10.1016%2fj.freeradbiomed.2022.10.315&partnerID=40&md5=b15934c34d5ef482f3bf893ed9ce98daFREE RADICAL BIOLOGY AND MEDICINEISSN: 08915849ISSNe: 18734596reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p148742026-06-14T12:41:47Z
dc.title.none.fl_str_mv DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
title DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
spellingShingle DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
Gallinat, A
DJ-1
PARK7
Ischemia
reperfusion
RNA-Binding
Mitochondria
title_short DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
title_full DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
title_fullStr DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
title_full_unstemmed DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
title_sort DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion
dc.creator.none.fl_str_mv Gallinat, A
Rakovic, A
Klein, C
Badimon, L
author Gallinat, A
author_facet Gallinat, A
Rakovic, A
Klein, C
Badimon, L
author_role author
author2 Rakovic, A
Klein, C
Badimon, L
author2_role author
author
author
dc.subject.none.fl_str_mv DJ-1
PARK7
Ischemia
reperfusion
RNA-Binding
Mitochondria
topic DJ-1
PARK7
Ischemia
reperfusion
RNA-Binding
Mitochondria
description The early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been identified. However, no functional charac-terization has been provided to date. Here, we have investigated the DJ-1-interacting transcripts, as well as the role of DJ-1 RNA-binding activity during ischemia and reperfusion. Among the identified DJ-1-interacting transcripts, we have distinguished a significant enrichment of mRNAs encoding mitochondrial proteins. The effects of DJ-1 depletion on mitochondrial protein expression and mitochondrial morphology were investigated using a CRISPR/Cas9 generated DJ-1 knockout (DJ-1KO) cell model. DJ-1 depletion resulted in increased MTND2 protein expression in resting cells; however, after exposure to I/R, MTND2 levels were significantly reduced with respect to wild type cells. Increased mitochondrial fission was consistently found in DJ-1KO cells after I/R exposure. MTND2 transcript binding to DJ-1 was increased during ischemia. Our results indicate that the RNA -binding activity of DJ-1 shield mitochondrial transcripts from oxidative damage.
publishDate 2022
dc.date.none.fl_str_mv 2022
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14874
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143379982&doi=10.1016%2fj.freeradbiomed.2022.10.315&partnerID=40&md5=b15934c34d5ef482f3bf893ed9ce98da
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14874
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143379982&doi=10.1016%2fj.freeradbiomed.2022.10.315&partnerID=40&md5=b15934c34d5ef482f3bf893ed9ce98da
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER SCIENCE INC
publisher.none.fl_str_mv ELSEVIER SCIENCE INC
dc.source.none.fl_str_mv FREE RADICAL BIOLOGY AND MEDICINE
ISSN: 08915849
ISSNe: 18734596
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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