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

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

Stable Identifier

R-HSA-8949178

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

ReviewStatus

5/5

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

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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 Sancak, Y, Markhard, AL, Kitami, T, Kovács-Bogdán, E, Kamer, KJ, Udeshi, ND, Carr, SA, Chaudhuri, D, Clapham, DE, Li, AA, Calvo, SE, Goldberger, O, Mootha, VK	Science	2013
23755363	MCU encodes the pore conducting mitochondrial calcium currents Chaudhuri, D, Sancak, Y, Mootha, VK, Clapham, DE	Elife	2013
20693986	MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake Perocchi, F, Gohil, VM, Girgis, HS, Bao, XR, McCombs, JE, Palmer, AE, Mootha, VK	Nature	2010
23900286	The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit Raffaello, A, De Stefani, D, Sabbadin, D, Teardo, E, Merli, G, Picard, A, Checchetto, V, Moro, S, Szabò, I, Rizzuto, R	EMBO J.	2013
26976564	Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition Chaudhuri, D, Artiga, DJ, Abiria, SA, Clapham, DE	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 Paupe, V, Prudent, J, Dassa, EP, Rendon, OZ, Shoubridge, EA	Cell Metab.	2015
21685888	A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter De Stefani, D, Raffaello, A, Teardo, E, Szabò, I, Rizzuto, R	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 Tsai, MF, Phillips, CB, Ranaghan, M, Tsai, CW, Wu, Y, Willliams, C, Miller, C	Elife	2016
25753332	Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death Liao, Y, Hao, Y, Chen, H, He, Q, Yuan, Z, Cheng, J	Protein Cell	2015
21685886	Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter Baughman, JM, Perocchi, F, Girgis, HS, Plovanich, M, Belcher-Timme, CA, Sancak, Y, Bao, XR, Strittmatter, L, Goldberger, O, Bogorad, RL, Koteliansky, V, Mootha, VK	Nature	2011
23409044	MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling Plovanich, M, Bogorad, RL, Sancak, Y, Kamer, KJ, Strittmatter, L, Li, AA, Girgis, HS, Kuchimanchi, S, De Groot, J, Speciner, L, Taneja, N, Oshea, J, Koteliansky, V, Mootha, VK	PLoS ONE	2013
24560927	MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity Patron, M, Checchetto, V, Raffaello, A, Teardo, E, Vecellio Reane, D, Mantoan, M, Granatiero, V, Szabò, I, De Stefani, D, Rizzuto, R	Mol. Cell	2014
24162235	Mitochondrial Ca(2+) uniporter (MCU)-dependent and MCU-independent Ca(2+) channels coexist in the inner mitochondrial membrane Bondarenko, AI, Jean-Quartier, C, Parichatikanond, W, Alam, MR, Waldeck-Weiermair, M, Malli, R, Graier, WF	Pflugers Arch.	2014
7399049	The role of calcium in the regulation of mitochondrial metabolism Denton, RM, McCormack, JG	Biochem. Soc. Trans.	1980