The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state.
C. elegans
Calcium signaling
MCU
Mitochondria
Redox biology
Skeletal muscle
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
21
04
2023
revised:
14
05
2023
accepted:
21
05
2023
medline:
12
7
2023
pubmed:
12
6
2023
entrez:
11
6
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37302345
pii: S2213-2317(23)00160-X
doi: 10.1016/j.redox.2023.102759
pmc: PMC10363449
pii:
doi:
Substances chimiques
Calcium
SY7Q814VUP
mitochondrial calcium uniporter
0
Mcu-1 protein, C elegans
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102759Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.W., A.H., F.B. , F.S., S.K., V.S., J.N.F and J. U.D.M. are or were employees of Nestlé Research, which is part of the Société des Produits Nestlé SA.
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