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Calcium uniporter protein, mitochondrial

Definition:

Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex). Activity is regulated by MICU1 and MICU2. At low Ca(2+) levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes. While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells. participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake. Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity). Involved in antigen processing and presentation (By similarity).

References:

[1]. Dipayan Chaudhuri, et al. MCU encodes the pore conducting mitochondrial calcium currents. Elife. 2013 Jun 4;2:e00704. [Content Brief]

[2]. Yuejin Wu, et al. The mitochondrial uniporter controls fight or flight heart rate increases. Nat Commun. 2015 Jan 20;6:6081. [Content Brief]

[3]. Nicholas E Hoffman, et al. MICU1 motifs define mitochondrial calcium uniporter binding and activity. Cell Rep. 2013 Dec 26;5(6):1576-1588. [Content Brief]

[4]. Jessica Matesanz-Isabel, et al. Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake. Biochim Biophys Acta. 2016 Jun;1858(6):1110-7. [Content Brief]

[5]. Youngjin Lee, et al. Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter. EMBO Rep. 2015 Oct;16(10):1318-33. [Content Brief]

[6]. Diego De Stefani, et al. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 2011 Jun 19;476(7360):336-40. [Content Brief]

[7]. Andrei I Tarasov, et al. The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic β-cells. PLoS One. 2012;7(7):e39722. [Content Brief]

[8]. Maria Patron, et al. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell. 2014 Mar 6;53(5):726-37. [Content Brief]

[9]. Joshua M Baughman, et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 2011 Jun 19;476(7360):341-5. [Content Brief]

[10]. Ilaria Drago, et al. Mitochondrial Ca2+ uptake contributes to buffering cytoplasmic Ca2+ peaks in cardiomyocytes. Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12986-91. [Content Brief]

[11]. Karthik Mallilankaraman, et al. MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat Cell Biol. 2012 Dec;14(12):1336-43. [Content Brief]

[12]. Karthik Mallilankaraman, et al. MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell. 2012 Oct 26;151(3):630-44. [Content Brief]

[13]. Muhammad Rizwan Alam, et al. Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU) contribute to metabolism-secretion coupling in clonal pancreatic β-cells. J Biol Chem. 2012 Oct 5;287(41):34445-54. [Content Brief]

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