RT info:eu-repo/semantics/article
T1 The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state
A1 Weiser, Anna
A1 Hermant, Aurélie
A1 Bermont, Flavien
A1 Sizzano, Federico
A1 Karaz, Sonia
A1 Alvarez-Illera, Pilar
A1 Santo-Domingo, Jaime
A1 Sorrentino, Vincenzo
A1 Feige, Jerome N.
A1 De Marchi, Umberto
AB 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.
SN 2213-2317
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/73919
UL https://uvadoc.uva.es/handle/10324/73919
LA eng
NO Weiser A, Hermant A, Bermont F, Sizzano F, Karaz S, Alvarez-Illera P, Santo-Domingo J, Sorrentino V, Feige JN, De Marchi U. The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state. Redox Biol. 2023 Aug;64:102759. doi: 10.1016/j.redox.2023.102759. Epub 2023 Jun 4. PMID: 37302345; PMCID: PMC10363449.
DS UVaDOC
RD 22-ene-2025