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...

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Published in:Redox biology 2023-08, Vol.64, p.102759-102759, Article 102759
Main Authors: Weiser, Anna, Hermant, Aurélie, Bermont, Flavien, Sizzano, Federico, Karaz, Sonia, Alvarez-Illera, Pilar, Santo-Domingo, Jaime, Sorrentino, Vincenzo, Feige, Jerome N., De Marchi, Umberto
Format: Article
Language:English
Subjects:
Animals
C. elegans
Caenorhabditis elegans - metabolism
Calcium - metabolism
Calcium signaling
Humans
MCU
Mitochondria
Mitochondria - metabolism
Oxidation-Reduction
Redox biology
Research Paper
Respiration
Skeletal muscle
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Summary: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. [Display omitted]
ISSN:2213-2317
2213-2317
DOI:10.1016/j.redox.2023.102759