The molecular complexity of the Mitochondrial Calcium Uniporter

Feno, Simona; Meneghesso, Gaudenzio; Raffaello, Anna; Reane, Denis Vecellio

doi:10.1016/j.ceca.2020.102322

Cited by 34 publications

(36 citation statements)

References 78 publications

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“…Using our RNAseq data set, we delved into the expression of genes encoding for different regulators of intracellular calcium signaling: IP3R, SERCA, ORAI channels, and the mitochondrial calcium uniporter (MCU). The MCU holoplex consists of the MCU ion pore, its negative regulatory subunit MCUb, the essential regulator Smdt1/ EMRE, the two regulatory subunits MICU1 and MICU2 (and the CNS paralogue MICU3), and the MICUR1 regulator [46]. This analysis showed Ca 2+ genes were upregulated in the DN3-DN4 transition, and that deletion of Opa1 had no effect on the expression of these studied genes.…”

Section: Opa1-deficient Thymocytes Are More Susceptible To Tcr Stimulmentioning

confidence: 91%

Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism

et al. 2021

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Optic atrophy 1 (OPA1), a mitochondria-shaping protein controlling cristae biogenesis and respiration, is required for memory T cell function, but whether it affects intrathymic T cell development is unknown. Here we show that OPA1 is necessary for thymocyte maturation at the double negative (DN)3 stage when rearrangement of the T cell receptor β (Tcrβ) locus occurs. By profiling mitochondrial function at different stages of thymocyte maturation, we find that DN3 cells rely on oxidative phosphorylation. Consistently, Opa1 deletion during early T cell development impairs respiration of DN3 cells and reduces their number. Opa1-deficient DN3 cells indeed display stronger TCR signaling and are more prone to cell death. The surviving Opa1−/− thymocytes that reach the periphery as mature T cells display an effector memory phenotype even in the absence of antigenic stimulation but are unable to generate metabolically fit long-term memory T cells. Thus, mitochondrial defects early during T cell development affect mature T cell function.

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Section: Opa1-deficient Thymocytes Are More Susceptible To Tcr Stimulmentioning

confidence: 91%

Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism

et al. 2021

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“…Mitochondria not only are the powerhouse of the cells but also participate in many regulatory functions, among them Ca 2+ homeostasis. Mitochondria can take up Ca 2+ through a highly sophisticated channel, the mitochondrial calcium uniporter (MCU) complex ( Baughman et al., 2011 ; Feno et al., 2021 ; Patron et al., 2014 ; De Stefani et al., 2011 ). Furthermore, in the last decade, evidence has emerged showing that mitochondria contribute to the regulation of fiber size ( Mammucari et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Parvalbumin affects skeletal muscle trophism through modulation of mitochondrial calcium uptake

et al. 2021

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Summary Parvalbumin (PV) is a cytosolic Ca 2+ -binding protein highly expressed in fast skeletal muscle, contributing to an increased relaxation rate. Moreover, PV is an “atrogene” downregulated in most muscle atrophy conditions. Here, we exploit mice lacking PV to explore the link between the two PV functions. Surprisingly, PV ablation partially counteracts muscle loss after denervation. Furthermore, acute PV downregulation is accompanied by hypertrophy and upregulation by atrophy. PV ablation has a minor impact on sarcoplasmic reticulum but is associated with increased mitochondrial Ca 2+ uptake, mitochondrial size and number, and contacts with Ca 2+ release sites. Mitochondrial calcium uniporter (MCU) silencing abolishes the hypertrophic effect of PV ablation, suggesting that mitochondrial Ca 2+ uptake is required for hypertrophy. In turn, an increase of mitochondrial Ca 2+ is required to enhance expression of the pro-hypertrophy gene PGC-1α4, whose silencing blocks hypertrophy due to PV ablation. These results reveal how PV links cytosolic Ca 2+ control to mitochondrial adaptations, leading to muscle mass regulation.

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“…In macrophages, transient increases in cytosolic Ca 2+ ([Ca 2+ ] cyt ) are frequently observed during the course of phagosome formation (14)(15)(16)(17), but the role of mitochondrial Ca 2+ remains controversial (14,18). Mitochondrial Ca 2+ regulates many cell functions, from stimulating aerobic metabolism and thus adenosine 5′-triphosphate (ATP) production under normal conditions to the induction of cell death under pathological conditions (19). The discovery of the molecular identity of the mitochondrial calcium uniporter (MCU) complex (20,21), the highly selective channel responsible for mitochondrial Ca 2+ entry, gave rise to studies that aimed to clarify not only the composition and the regulation of the MCU complex but also the pathophysiological role of mitochondrial Ca 2+ uptake (22).…”

Section: Introductionmentioning

confidence: 99%

The dominant-negative mitochondrial calcium uniporter subunit MCUb drives macrophage polarization during skeletal muscle regeneration

et al. 2021

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The molecular complexity of the Mitochondrial Calcium Uniporter

Cited by 34 publications

References 78 publications

Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism

Deletion of the mitochondria-shaping protein Opa1 during early thymocyte maturation impacts mature memory T cell metabolism

Parvalbumin affects skeletal muscle trophism through modulation of mitochondrial calcium uptake

The dominant-negative mitochondrial calcium uniporter subunit MCUb drives macrophage polarization during skeletal muscle regeneration

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