Molecular regulation of MCU: Implications in physiology and disease

Cell Calcium

Volumn 74, Issue , 2018, Pages 86-93

  Nemani, Neeharika ^a   Shanmughapriya, Santhanam ^a   Madesh, Muniswamy ^a,b  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

Calcium; Channel; EMRE; Magnesium; MCU; MCUb; MCUR1; MICU1; Miro1; MiST; Mitochondria; Oxidants; SLC25A23

Indexed keywords

CALCIUM; DIVALENT CATION; GLYCOSAMINOGLYCAN; INWARDLY RECTIFYING POTASSIUM CHANNEL; NICOTINIC ACID ADENINE DINUCLEOTIDE PHOSPHATE; PHOSPHOLIPID; CALCIUM CHANNEL; CARRIER PROTEIN; MITOCHONDRIAL CALCIUM UNIPORTER;

AMINO TERMINAL SEQUENCE; APOPTOSIS; BIOENERGY; CALCIUM SIGNALING; CALCIUM TRANSPORT; CARBOXY TERMINAL SEQUENCE; CELL DEATH; CELL FATE; CELL SURVIVAL; CYTOPLASM; HUMAN; MEMBRANE POTENTIAL; MITOCHONDRIAL MEMBRANE; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; PRIORITY JOURNAL; PROTEIN PROCESSING; REVIEW; SECOND MESSENGER; TRANSCRIPTION REGULATION; ANIMAL; CELL FUNCTION; CHEMISTRY; CYTOSOL; METABOLISM; MITOCHONDRIAL MEMBRANE POTENTIAL; PHYSIOLOGY;

ANIMALS; CALCIUM; CALCIUM CHANNELS; CELL DEATH; CELL PHYSIOLOGICAL PHENOMENA; CYTOSOL; HUMANS; MEMBRANE POTENTIAL, MITOCHONDRIAL; MITOCHONDRIA; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIAL MEMBRANES;

EID: 85049352289     PISSN: 01434160     EISSN: 15321991     Source Type: Journal    
DOI: 10.1016/j.ceca.2018.06.006     Document Type: Review

References (95)

1. Berridge, M.J., Lipp, P., Bootman, M.D., The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol., 1, 2000 p. 11.
2. Berridge, M.J., Bootman, M.D., Roderick, H.L., Calcium: calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 4 (2003), 517–529.
3. Penner, R., Fasolato, C., Hoth, M., Calcium influx and its control by calcium release. Curr. Opin. Neurobiol. 3:3 (1993), 368–374.
4. Putney, J.W., McKay, R.R., Capacitative calcium entry channels. BioEssays 21:1 (1999), 38–46.
5. Gunter, T.E., Pfeiffer, D.R., Mechanisms by which mitochondria transport calcium. Am. J. Physiol., 258(5 Pt 1), 1990 p. C755-86.
6. Glancy, B., Balaban, R.S., Role of mitochondrial Ca2+in the regulation of cellular energetics. Biochemistry 51 (2012), 2959–2973.
7. Hoth, M., Fanger, C.M., Lewis, R.S., Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J. Cell. Biol. 137:3 (1997), 633–648.
8. Gilabert, J.A., Parekh, A.B., Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca(2+) current I(CRAC). EMBO J. 19:23 (2000), 6401–6407.
9. Lemasters, J.J., et al. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim. Biophys. Acta 1366:1-2 (1998), 177–196.
10. Nakagawa, T., et al. Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434:7033 (2005), 652–658.
11. Baughman, J.M., et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476 (2011), 341–345.
12. De Stefani, D., et al. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:7360 (2011), 336–340.
13. Luft, J.H., Ruthenium red and violet. I. Chemistry, purification, methods of use for electron microscopy and mechanism of action. Anat. Rec. 171:3 (1971), 347–368.
14. Reed, K.C., Bygrave, F.L., The inhibition of mitochondrial calcium transport by lanthanides and ruthenium Red. Biochem. J. 140:2 (1974), 143–155.
15. Kirichok, Y., Krapivinsky, G., Clapham, D.E., The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427 (2004), 360–364.
16. Kovacs-Bogdan, E., et al. Reconstitution of the mitochondrial calcium uniporter in yeast. Proc. Natl. Acad. Sci. U. S. A. 111:24 (2014), 8985–8990.
17. Lee, Y., et al. Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter. EMBO Rep. 16:10 (2015), 1318–1333.
18. Lee, S.K., et al. Structural insights into mitochondrial calcium uniporter regulation by divalent cations. Cell. Chem. Biol. 23 (2016), 1157–1169.
19. Oxenoid, K., et al. Architecture of the mitochondrial calcium uniporter. Nature 533:7602 (2016), 269–273.
20. Mallilankaraman, K., et al. MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat. Cell. Biol. 14:12 (2012), 1336–1343.
21. Perocchi, F., Gohli, V., Girgis, H.S., Bao, X.R., McCombs, J.E., Palmer, A.E., Mootha, V.K., MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature, 2010.
22. Plovanich, M., et al. MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One, 8(2), 2013 p. e55785.
23. Yasemin Sancak, A.L.M., Kitami, Toshimori, Kovács-Bogdán, Erika, Kamer, Kimberli J., Udeshi, Namrata D., Carr, Steven A., Chaudhuri, Dipayan, Clapham, David E., Li, Andrew A., Calvo, Sarah E., Goldberger, Olga, Mootha, Vamsi K., EMRE Is an essential component of the mitochondrial calcium uniporter complex. Science, 342, 2013.
24. Hoffman, N.E., et al. SLC25A23 augments mitochondrial Ca(2)(+) uptake, interacts with MCU, and induces oxidative stress-mediated cell death. Mol. Biol. Cell. 25:6 (2014), 936–947.
25. Raffaello, A., et al. The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J. 32:17 (2013), 2362–2376.
26. Mallilankaraman, K., et al. MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell 151:3 (2012), 630–644.
27. + uniporter. Cell Metab., 2013.
28. Hoffman, N.E., et al. MICU1 motifs define mitochondrial calcium uniporter binding and activity. Cell. Rep. 5:6 (2013), 1576–1588.
29. Wang, L., et al. Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake. EMBO J. 33:6 (2014), 594–604.
30. Liu, J.C., et al. MICU1 serves as a molecular gatekeeper to prevent in vivo mitochondrial calcium overload. Cell. Rep. 16:6 (2016), 1561–1573.
31. Logan, C.V., et al. Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling. Nat. Genet 46:2 (2014), 188–193.
32. Bhosale, G., et al. Pathological consequences of MICU1 mutations on mitochondrial calcium signalling and bioenergetics. Biochim. Biophys. Acta 1864:6 (2017), 1009–1017.
33. Antony, A.N., et al. MICU1 regulation of mitochondrial Ca(2+) uptake dictates survival and tissue regeneration. Nat. Commun., 7, 2016 p. 10955.
34. Kamer, K.J., Mootha, V.K., MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter. EMBO Rep. 15:3 (2014), 299–307.
35. Bick, A.G., et al. Cardiovascular homeostasis dependence on MICU2, a regulatory subunit of the mitochondrial calcium uniporter. Proc. Natl. Acad. Sci. U. S. A. 114:43 (2017), E9096–E9104.
36. Kamer, K.J., Grabarek, Z., Mootha, V.K., High-affinity cooperative Ca(2+) binding by MICU1-MICU2 serves as an on-off switch for the uniporter. EMBO Rep. 18:8 (2017), 1397–1411.
37. Vais, H., et al. MCUR1, CCDC90A, Is a regulator of the mitochondrial calcium uniporter. Cell. Metab. 22:4 (2015), 533–535.
38. Paupe, V., et al. CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter. Cell. Metab. 21:1 (2015), 109–116.
39. Tomar, D., et al. MCUR1 Is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics. Cell. Rep. 15:8 (2016), 1673–1685.
40. Chaudhuri, D., et al. Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium threshold for the mitochondrial permeability transition. Proc. Natl. Acad. Sci. U. S. A. 113:13 (2016), E1872–80.
41. Vais, H., et al. EMRE Is a matrix Ca(2+) sensor that governs gatekeeping of the mitochondrial Ca(2+) uniporter. Cell. Rep. 14:3 (2016), 403–410.
42. Yamamoto, T., et al. Analysis of the structure and function of EMRE in a yeast expression system. Biochim. Biophys. Acta 1857:6 (2016), 831–839.
43. Hajnóczky, G., et al. Decoding of cytosolic calcium oscillations in the mitochondria. Cell 82:3 (1995), 415–424.
44. Robb-Gaspers, L.D., et al. Integrating cytosolic calcium signals into mitochondrial metabolic responses. EMBO J. 17:17 (1998), 4987–5000.
45. Duchen, M.R., Mitochondria and calcium: from cell signalling to cell death. J. Physiol. 529:Pt 1 (2000), 57–68.
46. Berridge, M.J., Bootman, M.D., Roderick, H.L., Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell. Biol. 4:7 (2003), 517–529.
47. Hogan, P.G., Lewis, R.S., Rao, A., Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu. Rev. Immunol. 28 (2010), 491–533.
48. Feske, S., et al. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:7090 (2006), 179–185.
49. Roos, J., et al. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J. Cell. Biol. 169:3 (2005), 435–445.
50. Zhang, S.L., et al. Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity. Proc. Natl. Acad. Sci. U. S. A 103:24 (2006), 9357–9362.
51. Liou, J., et al. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr. Biol. 15:13 (2005), 1235–1241.
52. Luik, R.M., et al. Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation. Nature 454:7203 (2008), 538–542.
53. McNally, B.A., et al. Gated regulation of CRAC channel ion selectivity by STIM1. Nature 482:7384 (2012), 241–245.
54. Shanmughapriya, S., et al. Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU. Sci. Signal., 8(366), 2015 p. ra23.
55. Filipowicz, W., Bhattacharyya, S.N., Sonenberg, N., Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat. Rev. Genet 9:2 (2008), 102–114.
56. Marchi, S., et al. Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25. Curr. Biol. 23:1 (2013), 58–63.
57. Hong, Z., et al. MicroRNA-138 and MicroRNA-25 down-regulate mitochondrial calcium uniporter, causing the pulmonary arterial hypertension cancer phenotype. Am. J. Respir. Crit. Care Med. 195:4 (2017), 515–529.
58. Yu, C., et al. Mitochondrial calcium uniporter as a target of microRNA-340 and promoter of metastasis via enhancing the Warburg effect. Oncotarget 8:48 (2017), 83831–83844.
59. Zaglia, T., et al. Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy. Proc. Natl. Acad. Sci. U. S. A. 114:43 (2017), E9006–E9015.
60. Carafoli, E., The fateful encounter of mitochondria with calcium: how did it happen?. Biochim. Biophys. Acta 1797:6-7 (2010), 595–606.
61. Brierley, G.P., Murer, E., Bachmann, E., Studies on ion transport. III. The accumulation of calcium and inorganic phosphate by heart mitochondria. Arch. Biochem. Biophys. 105 (1964), 89–102.
62. Fiermonte, G., Dolce, V., Palmieri, F., Expression in Escherichia coli, functional characterization, and tissue distribution of isoforms a and B of the phosphate carrier from bovine mitochondria. J. Biol. Chem. 273:35 (1998), 22782–22787.
63. Deluca, H.F., Engstrom, G.W., Calcium uptake by rat kidney mitochondria. Proc. Natl. Acad. Sci. U. S. A. 47 (1961), 1744–1750.
64. Rossi, C.S., Lehninger, A.L., Stoichiometry of respiratory stimulation, accumulation of CA++ and phosphate, and oxidative phosphorylation in rat liver mitochondria. J. Biol. Chem. 239 (1964), 3971–3980.
65. Zoeteweij, J.P., et al. Calcium-induced cytotoxicity in hepatocytes after exposure to extracellular ATP is dependent on inorganic phosphate. Effects on mitochondrial calcium. J. Biol. Chem. 268:5 (1993), 3384–3388.
66. Mayr, J.A., et al. Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. Am. J. Hum. Genet. 80:3 (2007), 478–484.
67. Mayr, J.A., et al. Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children. Neuromuscul. Disord. 21:11 (2011), 803–808.
68. Bhoj, E.J., et al. Pathologic variants of the mitochondrial phosphate carrier SLC25A3: Two New patients and expansion of the Cardiomyopathy/Skeletal myopathy phenotype with and without lactic acidosis. JIMD Rep. 19 (2015), 59–66.
69. Seifert, E.L., et al. Natural and induced mitochondrial phosphate carrier loss: DIFFERENTIAL DEPENDENCE OF mitochondrial metabolism and dynamics and cell survival on the extent of depletion. J. Biol. Chem. 291:50 (2016), 26126–26137.
70. Kwong, J.Q., et al. Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy. Cell. Death Differ. 21:8 (2014), 1209–1217.
71. Gutiérrez-Aguilar, M., et al. Genetic manipulation of the cardiac mitochondrial phosphate carrier does not affect permeability transition. J. Mol. Cell. Cardiol. 72 (2014), 316–3255.
72. Buttgereit, F., Brand, M.D., A hierarchy of ATP-consuming processes in mammalian cells. Biochem. J. 312:Pt 1 (1995), 163–167.
73. Fiermonte, G., et al. Identification of the mitochondrial ATP-Mg/Pi transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution. J. Biol. Chem. 279:29 (2004), 30722–30730.
74. Aprille, J.R., Regulation of the mitochondrial adenine nucleotide pool size in liver: mechanism and metabolic role. FASEB J. 2:10 (1988), 2547–2556.
75. Palmieri, F., The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol. Aspects Med. 34:2-3 (2013), 465–484.
76. Tewari, S.G., et al. A biophysical model of the mitochondrial ATP-Mg/P(i) carrier. Biophys. J. 103:7 (2012), 1616–1625.
77. Amigo, I., et al. Glucagon regulation of oxidative phosphorylation requires an increase in matrix adenine nucleotide content through Ca2+ activation of the mitochondrial ATP-Mg/Pi carrier SCaMC-3. J. Biol. Chem. 288:11 (2013), 7791–7802.
78. Theillet, F.X., et al. Cell signaling, post-translational protein modifications and NMR spectroscopy. J. Biomol. NMR 54:3 (2012), 217–236.
79. Brewer, T.F., et al. Chemical approaches to discovery and study of sources and targets of hydrogen peroxide redox signaling through NADPH oxidase proteins. Annu. Rev. Biochem. 84 (2015), 765–790.
80. Joiner, M.L., et al. CaMKII determines mitochondrial stress responses in heart. Nature 491:7423 (2012), 269–273.
81. Davidson, S.M., et al. Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore. Cardiovasc. Res. 108:3 (2015), 357–366.
82. Bernardi, P., Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol. Rev. 79:4 (1999), 1127–1155.
83. Halestrap, A.P., Griffiths, E.J., Connern, C.P., Mitochondrial calcium handling and oxidative stress. Biochem. Soc. Trans. 21:2 (1993), 353–358.
84. Kroemer, G., Galluzzi, L., Brenner, C., Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87:1 (2007), 99–163.
85. Newmeyer, D.D., Ferguson-Miller, S., Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112:4 (2003), 481–490.
86. Orrenius, S., Zhivotovsky, B., Nicotera, P., Regulation of cell death: the calcium-apoptosis link. Nat. Rev. Mol. Cell. Biol. 4:7 (2003), 552–565.
87. Pan, X., et al. The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter. Nat. Cell. Biol. 15:12 (2013), 1464–1472.
88. Luongo, T.S., et al. The mitochondrial calcium uniporter matches energetic supply with cardiac workload during stress and modulates permeability transition. Cell. Rep. 12:1 (2015), 23–34.
89. Voth, J.B.-H.A.M., Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. Microsc. Res. Tech., 1994.
90. Youle, M.Ka.R., Dynamics of mitochondrial morphology in healthy cells and during apoptosis. Cell. Death Differ., 2003.
91. Youle, R.J., van der Bliek, A.M., Mitochondrial fission, fusion, and stress. Science 337:6098 (2012), 1062–1065.
92. Yaffe, M.P., The machinery of mitochondrial inheritance and behavior. Science 283:5407 (1999), 1493–1497.
93. Mishra, P., Chan, D.C., Mitochondrial dynamics and inheritance during cell division, development and disease. Nat. Rev. Mol. Cell. Biol. 15:10 (2014), 634–646.
94. McArthur, K.W., Whitehead, L., Heddleston, J.M., Li, L., Padman, B.S., Oorschot, V., Geoghegan, N.D., Chappaz, Davidson, S., San Chin, H., Lane, R.M., Dramicanin, M., Saunders, T.L., Sugiana, C., Lessene, R., Osellame, L.D., Chew, T.L., Dewson, G., Lazarou, M., Ramm, G., Lessene, G., Ryan, M.T., Rogers, K.L., van Delft, M.F., Kile, B.T., BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science, 359, 2018, 6378.
95. Nemani, N., et al. MIRO-1 determines mitochondrial shape transition upon GPCR activation and Ca(2+) stress. Cell. Rep. 23:4 (2018), 1005–1019.