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Open AccessArticle

The Function of Mitochondrial Calcium Uniporter at the Whole-Cell and Single Mitochondrion Levels in WT, MICU1 KO, and MICU2 KO Cells

Department of Physics, University of South Florida, Tampa, FL 33647, USA
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Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1520; https://doi.org/10.3390/cells9061520
Received: 14 May 2020 / Revised: 15 June 2020 / Accepted: 16 June 2020 / Published: 22 June 2020
(This article belongs to the Special Issue Dysregulation of Calcium Signalling in Disease)
Mitochondrial Ca2+ ([Ca2+]M) uptake through its Ca2+ uniporter (MCU) is central to many cell functions such as bioenergetics, spatiotemporal organization of Ca2+ signals, and apoptosis. MCU activity is regulated by several intrinsic proteins including MICU1, MICU2, and EMRE. While significant details about the role of MICU1, MICU2, and EMRE in MCU function have emerged recently, a key challenge for the future experiments is to investigate how these regulatory proteins modulate mitochondrial Ca2+ influx through MCU in intact cells under pathophysiological conditions. This is further complicated by the fact that several variables affecting MCU function change dynamically as cell functions. To overcome this void, we develop a data-driven model that closely replicates the behavior of MCU under a wide range of cytosolic Ca2+ ([Ca2+]C), [Ca2+]M, and mitochondrial membrane potential values in WT, MICU1 knockout (KO), and MICU2 KO cells at the single mitochondrion and whole-cell levels. The model is extended to investigate how MICU1 or MICU2 KO affect mitochondrial function. Moreover, we show how Ca2+ buffering proteins, the separation between mitochondrion and Ca2+-releasing stores, and the duration of opening of Ca2+-releasing channels affect mitochondrial function under different conditions. Finally, we demonstrate an easy extension of the model to single channel function of MCU. View Full-Text
Keywords: mitochondrial Ca2+ uptake; mitochondrial Ca2+ uniporter; MICU1; MICU2; EMRE; Ca2+ overload mitochondrial Ca2+ uptake; mitochondrial Ca2+ uniporter; MICU1; MICU2; EMRE; Ca2+ overload
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MDPI and ACS Style

Shah, S.I.; Ullah, G. The Function of Mitochondrial Calcium Uniporter at the Whole-Cell and Single Mitochondrion Levels in WT, MICU1 KO, and MICU2 KO Cells. Cells 2020, 9, 1520. https://doi.org/10.3390/cells9061520

AMA Style

Shah SI, Ullah G. The Function of Mitochondrial Calcium Uniporter at the Whole-Cell and Single Mitochondrion Levels in WT, MICU1 KO, and MICU2 KO Cells. Cells. 2020; 9(6):1520. https://doi.org/10.3390/cells9061520

Chicago/Turabian Style

Shah, Syed I.; Ullah, Ghanim. 2020. "The Function of Mitochondrial Calcium Uniporter at the Whole-Cell and Single Mitochondrion Levels in WT, MICU1 KO, and MICU2 KO Cells" Cells 9, no. 6: 1520. https://doi.org/10.3390/cells9061520

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