MCU translocates calcium from the mitochondrial intermembrane space to the mitochondrial matrix

Stable Identifier
Reaction [transition]
Homo sapiens
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The mitochondrial calcium uniporter (MCU) is a protein complex located in the mitochondrial inner membrane that transports divalent calcium ions (Ca2+) from the mitochondrial intermembrane space, across the mitochondrial inner membrane, and into the mitochondrial matrix (De Stefani et al. 2011, Baughman et al. 2011, Chaudhuri et al. 2013) where the Ca2+ allosterically regulates matrix enzymes such as pyruvate dehydrogenase, isocitrate dehydrogenase, and the 2-oxoglutarate dehydrogenase complex (Denton and McCormack 1980). The MCU subunit of the complex forms the actual pore in the inner membrane and is suggested to interact with VDAC1 (Liao et al. 2015). MCUB is a differentially expressed paralog of MCU that is likewise located in the inner membrane but acts as an inhibitor of calcium import (Raffaello et al. 2013). MICU1 and MICU2 (or MICU3 in neurons) regulate the pore so that it opens only when cellular calcium concentrations are high (Perocchi et al. 2010, Plovanich et al. 2013, Patron et al. 2014, Kamer and Mootha et al. 2014). The SMDT1 (EMRE) subunit forms part of the pore and binds MICU1 and MICU2 (Sancak et al. 2013, Tsai et al. 2016). MCUR1 appears to associate with MCU, but its function is uncertain (Paupe et al. 2015, Chaudhuri et al. 2016). Other calcium channels are also detected in the mitochondrial inner membrane (Bondarenko et al. 2014).
Literature References
PubMed ID Title Journal Year
24231807 EMRE is an essential component of the mitochondrial calcium uniporter complex

Calvo, SE, Kovács-Bogdán, E, Clapham, DE, Mootha, VK, Carr, SA, Markhard, AL, Goldberger, O, Udeshi, ND, Sancak, Y, Kamer, KJ, Chaudhuri, D, Kitami, T, Li, AA

Science 2013
23755363 MCU encodes the pore conducting mitochondrial calcium currents

Clapham, DE, Sancak, Y, Chaudhuri, D, Mootha, VK

Elife 2013
20693986 MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake

Bao, XR, Perocchi, F, McCombs, JE, Girgis, HS, Mootha, VK, Palmer, AE, Gohil, VM

Nature 2010
23900286 The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit

Szabò, I, Sabbadin, D, Picard, A, Rizzuto, R, Teardo, E, Merli, G, Checchetto, V, De Stefani, D, Raffaello, A, Moro, S

EMBO J. 2013
26976564 Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition

Clapham, DE, Abiria, SA, Chaudhuri, D, Artiga, DJ

Proc. Natl. Acad. Sci. U.S.A. 2016
25565209 CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter

Prudent, J, Paupe, V, Rendon, OZ, Shoubridge, EA, Dassa, EP

Cell Metab. 2015
21685888 A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter

Szabò, I, Rizzuto, R, Teardo, E, Raffaello, A, De Stefani, D

Nature 2011
24503055 MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter

Kamer, KJ, Mootha, VK

EMBO Rep. 2014
27099988 Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex

Wu, Y, Phillips, CB, Miller, C, Willliams, C, Ranaghan, M, Tsai, MF, Tsai, CW

Elife 2016
25753332 Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death

Liao, Y, He, Q, Cheng, J, Hao, Y, Chen, H, Yuan, Z

Protein Cell 2015
21685886 Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter

Goldberger, O, Belcher-Timme, CA, Sancak, Y, Koteliansky, V, Baughman, JM, Bogorad, RL, Bao, XR, Perocchi, F, Girgis, HS, Strittmatter, L, Mootha, VK, Plovanich, M

Nature 2011
23409044 MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling

Speciner, L, Koteliansky, V, Bogorad, RL, Taneja, N, Girgis, HS, De Groot, J, Strittmatter, L, Mootha, VK, Plovanich, M, Oshea, J, Sancak, Y, Kamer, KJ, Kuchimanchi, S, Li, AA

PLoS ONE 2013
24560927 MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity

Szabò, I, Rizzuto, R, Mantoan, M, Granatiero, V, Teardo, E, Vecellio Reane, D, Checchetto, V, De Stefani, D, Raffaello, A, Patron, M

Mol. Cell 2014
24162235 Mitochondrial Ca(2+) uniporter (MCU)-dependent and MCU-independent Ca(2+) channels coexist in the inner mitochondrial membrane

Parichatikanond, W, Waldeck-Weiermair, M, Bondarenko, AI, Malli, R, Jean-Quartier, C, Graier, WF, Alam, MR

Pflugers Arch. 2014
7399049 The role of calcium in the regulation of mitochondrial metabolism

McCormack, JG, Denton, RM

Biochem. Soc. Trans. 1980
Catalyst Activity

calcium channel activity of MCU complex [mitochondrial inner membrane]

Orthologous Events
Cross References
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