The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state

Regulation of mitochondrial redox balance is emerging as a key event for cell signaling in both physiological and pathological conditions. However, the link between the mitochondrial redox state and the modulation of these conditions remains poorly defined. Here, we discovered that activation of the...

ver descrição completa

Detalhes bibliográficos
Autores: Weiser, Anna, Hermant, Aurélie, Bermont, Flavien, Sizzano, Federico, Karaz, Sonia, Alvarez-Illera, Pilar, Santo-Domingo, Jaime, Sorrentino, Vincenzo, Feige, Jerome N., Marchi, Umberto De
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/342565
Acesso em linha:http://hdl.handle.net/10261/342565
Access Level:Acceso aberto
Palavra-chave:Mitochondria
Calcium signaling
Redox biology
Skeletal muscle
MCU
C. elegans
id ES_fc7d5810e2105e9362aa83dffc1e6bdf
oai_identifier_str oai:digital.csic.es:10261/342565
network_acronym_str ES
network_name_str España
repository_id_str
spelling The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox stateWeiser, AnnaHermant, AurélieBermont, FlavienSizzano, FedericoKaraz, SoniaAlvarez-Illera, PilarSanto-Domingo, JaimeSorrentino, VincenzoFeige, Jerome N.Marchi, Umberto DeMitochondriaCalcium signalingRedox biologySkeletal muscleMCUC. elegansRegulation of mitochondrial redox balance is emerging as a key event for cell signaling in both physiological and pathological conditions. However, the link between the mitochondrial redox state and the modulation of these conditions remains poorly defined. Here, we discovered that activation of the evolutionary conserved mitochondrial calcium uniporter (MCU) modulates mitochondrial redox state. By using mitochondria-targeted redox and calcium sensors and genetic MCU-ablated models, we provide evidence of the causality between MCU activation and net reduction of mitochondrial (but not cytosolic) redox state. Redox modulation of redox-sensitive groups via MCU stimulation is required for maintaining respiratory capacity in primary human myotubes and C. elegans, and boosts mobility in worms. The same benefits are obtained bypassing MCU via direct pharmacological reduction of mitochondrial proteins. Collectively, our results demonstrate that MCU regulates mitochondria redox balance and that this process is required to promote the MCU-dependent effects on mitochondrial respiration and mobility.V.S. research is supported by the NUHS Internal Grant Funding under NUS Start-up grant NUHSRO/2022/047/Startup/11.ElsevierNational University of SingaporeConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/342565reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.redox.2023.102759Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3425652026-05-22T06:33:51Z
dc.title.none.fl_str_mv The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
title The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
spellingShingle The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
Weiser, Anna
Mitochondria
Calcium signaling
Redox biology
Skeletal muscle
MCU
C. elegans
title_short The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
title_full The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
title_fullStr The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
title_full_unstemmed The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
title_sort The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
dc.creator.none.fl_str_mv Weiser, Anna
Hermant, Aurélie
Bermont, Flavien
Sizzano, Federico
Karaz, Sonia
Alvarez-Illera, Pilar
Santo-Domingo, Jaime
Sorrentino, Vincenzo
Feige, Jerome N.
Marchi, Umberto De
author Weiser, Anna
author_facet Weiser, Anna
Hermant, Aurélie
Bermont, Flavien
Sizzano, Federico
Karaz, Sonia
Alvarez-Illera, Pilar
Santo-Domingo, Jaime
Sorrentino, Vincenzo
Feige, Jerome N.
Marchi, Umberto De
author_role author
author2 Hermant, Aurélie
Bermont, Flavien
Sizzano, Federico
Karaz, Sonia
Alvarez-Illera, Pilar
Santo-Domingo, Jaime
Sorrentino, Vincenzo
Feige, Jerome N.
Marchi, Umberto De
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National University of Singapore
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Mitochondria
Calcium signaling
Redox biology
Skeletal muscle
MCU
C. elegans
topic Mitochondria
Calcium signaling
Redox biology
Skeletal muscle
MCU
C. elegans
description Regulation of mitochondrial redox balance is emerging as a key event for cell signaling in both physiological and pathological conditions. However, the link between the mitochondrial redox state and the modulation of these conditions remains poorly defined. Here, we discovered that activation of the evolutionary conserved mitochondrial calcium uniporter (MCU) modulates mitochondrial redox state. By using mitochondria-targeted redox and calcium sensors and genetic MCU-ablated models, we provide evidence of the causality between MCU activation and net reduction of mitochondrial (but not cytosolic) redox state. Redox modulation of redox-sensitive groups via MCU stimulation is required for maintaining respiratory capacity in primary human myotubes and C. elegans, and boosts mobility in worms. The same benefits are obtained bypassing MCU via direct pharmacological reduction of mitochondrial proteins. Collectively, our results demonstrate that MCU regulates mitochondria redox balance and that this process is required to promote the MCU-dependent effects on mitochondrial respiration and mobility.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/342565
url http://hdl.handle.net/10261/342565
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.redox.2023.102759
Sí
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
_version_ 1869425427180683264
score 15,811543

Registros relacionados