Citations to this article
Abstract
The mitochondrial Ca2+ uniporter (MCU) complex mediates acute mitochondrial Ca2+ influx. In skeletal muscle, MCU links Ca2+ signaling to energy production by directly enhancing the activity of key metabolic enzymes in the mitochondria. Here, we examined the role of MCU in skeletal muscle development and metabolic function by generating mouse models for the targeted deletion of Mcu in embryonic, postnatal, and adult skeletal muscle. Loss of Mcu did not affect muscle growth and maturation or otherwise cause pathology. Skeletal muscle–specific deletion of Mcu in mice also did not affect myofiber intracellular Ca2+ handling, but it did inhibit acute mitochondrial Ca2+ influx and mitochondrial respiration stimulated by Ca2+, resulting in reduced acute exercise performance in mice. However, loss of Mcu also resulted in enhanced muscle performance under conditions of fatigue, with a preferential shift toward fatty acid metabolism, resulting in reduced body fat with aging. Together, these results demonstrate that MCU-mediated mitochondrial Ca2+ regulation underlies skeletal muscle fuel selection at baseline and under enhanced physiological demands, which affects total homeostatic metabolism.
Authors
Jennifer Q. Kwong, Jiuzhou Huo, Michael J. Bround, Justin G. Boyer, Jennifer A. Schwanekamp, Nasab Ghazal, Joshua T. Maxwell, Young C. Jang, Zaza Khuchua, Kevin Shi, Donald M. Bers, Jennifer Davis, Jeffery D. Molkentin
Total citations by year
Citations to this article in year 2023 (11)
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|---|---|---|
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Frontiers in physiology | 2023 |
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IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes
Sánchez-Aguilera P, López-Crisosto C, Norambuena-Soto I, Penannen C, Zhu J, Bomer N, Hoes MF, Van Der Meer P, Chiong M, Westenbrink BD, Lavandero S |
Frontiers in physiology | 2023 |
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The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation
García EF, Paudel U, Noji MC, Bowman CE, Pitarresi JR, Rustgi AK, Wellen KE, Arany Z, Weissenrieder JS, Foskett JK |
2023 | |
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Mitochondrial membrane potential instability on reperfusion after ischemia does not depend on mitochondrial Ca2+ uptake
Ashok D, Papanicolaou K, Sidor A, Wang M, Solhjoo S, Liu T, O\u2019Rourke B |
The Journal of biological chemistry | 2023 |
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The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation
Fernandez Garcia E, Paudel U, Noji MC, Bowman CE, Rustgi AK, Pitarresi JR, Wellen KE, Arany Z, Weissenrieder JS, Foskett JK |
Frontiers in Cell and Developmental Biology | 2023 |
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Energy (and Reactive Oxygen Species Generation) Saving Distribution of Mitochondria for the Activation of ATP Production in Skeletal Muscle.
Espinosa A, Casas M, Jaimovich E |
2023 | |
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Mitochondrial Properties in Skeletal Muscle Fiber
Dong H, Tsai SY |
Cells | 2023 |
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Beyond the TCA cycle: new insights into mitochondrial calcium regulation of oxidative phosphorylation.
Lee SH, Duron HE, Chaudhuri D |
Biochemical Society Transactions | 2023 |
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Distinct effects of cardiac mitochondrial calcium uniporter inactivation via EMRE deletion in the short and long term
Chapoy Villanueva H, Sung JH, Stevens JA, Zhang MJ, Nelson PM, Denduluri S, Feng F, O\u2019Connell TD, Townsend D, Liu JC |
Journal of Molecular and Cellular Cardiology | 2023 |
|
Microcirculation and Mitochondria: The Critical Unit
Wang G, Lian H, Zhang H, Wang X |
Journal of Clinical Medicine | 2023 |
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MCUb is an inducible regulator of calcium-dependent mitochondrial metabolism and substrate utilization in muscle.
Huo J, Prasad V, Grimes KM, Vanhoutte D, Blair NS, Lin SC, Bround MJ, Bers DM, Molkentin JD |
Cell Reports | 2023 |
