Calcium regulation of mitochondrial carriers

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1863, Issue 10, 2016, Pages 2413-2421

  del Arco, Araceli ^b,c,d   Contreras, Laura ^a,c,d   Pardo, Beatriz ^a,c,d   Satrustegui, Jorgina ^a,c,d  

^a CSIC   (Spain)

^b UNIVERSITY OF CASTILLA LA MANCHA   (Spain)

^c CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS CIBERER   (Spain)

^d UAM)   (Spain)

Author keywords

Aspartate glutamate carriers; ATP Mg2 + Pi carriers; Calcium; Mitochondrial carriers; Solute transport

Indexed keywords

ADENINE NUCLEOTIDE; ADENOSINE TRIPHOSPHATE MAGNESIUM PI EXCHANGER; ASPARTATE GLUTAMATE EXCHANGER; CALCIUM BINDING PROTEIN; CALCIUM ION; CALCIUM REGULATED MITOCHONDRIAL TRANSPORTER; CARRIER PROTEIN; MITOCHONDRIAL CALCIUM UNIPORTER; MITOCHONDRIAL PROTEIN; UNCLASSIFIED DRUG; ANTIPORTER; ARABIDOPSIS PROTEIN; ATP-MG-PI CARRIER PROTEINS, MITOCHONDRIA; CALCIUM; CITRIN; ORGANIC ANION TRANSPORTER; SACCHAROMYCES CEREVISIAE PROTEIN; SLC25A12 PROTEIN, HUMAN;

AMINO TERMINAL SEQUENCE; AUTISM; BINDING SITE; CALCIUM BINDING; CALCIUM HOMEOSTASIS; CARBOXY TERMINAL SEQUENCE; CITRIC ACID CYCLE; CITRULLINEMIA; CITRULLINEMIA TYPE II; GENE MUTATION; HUMAN; MITOCHONDRIAL BIOGENESIS; MITOCHONDRION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN MOTIF; REVIEW; UREA CYCLE; ACTIVE TRANSPORT; ANIMAL; CALCIUM SIGNALING; CELL RESPIRATION; DEFICIENCY; ION TRANSPORT; MAMMAL; METABOLISM; MITOCHONDRIAL MEMBRANE; MOLECULAR MODEL; PHYSIOLOGY; PROTEIN CONFORMATION;

ANIMALS; ANTIPORTERS; ARABIDOPSIS PROTEINS; BIOLOGICAL TRANSPORT, ACTIVE; CALCIUM; CALCIUM SIGNALING; CALCIUM-BINDING PROTEINS; CELL RESPIRATION; HUMANS; ION TRANSPORT; MAMMALS; MITOCHONDRIAL MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIAL MEMBRANES; MITOCHONDRIAL PROTEINS; MODELS, MOLECULAR; ORGANIC ANION TRANSPORTERS; PROTEIN CONFORMATION; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 84964370071     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2016.03.024     Document Type: Review

References (95)

1. Amigo, I., Traba, J., Satrústegui, J., del Arco, A., SCaMC-1Like a member of the mitochondrial carrier (MC) family preferentially expressed in testis and localized in mitochondria and chromatoid body. PLoS One, 7, 2012, e40470.
2. 2 + activation of the mitochondrial ATP-Mg/Pi carrier SCaMC-3. J. Biol. Chem. 288 (2013), 7791–7802.
3. 2 +/Pi transporter) reduces physical endurance and metabolic efficiency in mice. J. Biol. Chem. 286 (2011), 11659–11671.
4. Aprille, J.R., Mechanism and regulation of the mitochondrial ATP-Mg/P(i) carrier. J. Bioenerg. Biomembr. 25 (1993), 473–481.
5. Aprille, J.R., Nosek, M.T., Brennan, W.A. Jr., Adenine nucleotide content of liver mitochondria increases after glucagon treatment of rats or isolated hepatocytes. Biochem. Biophys. Res. Commun. 108 (1982), 834–839.
6. Bernardi, P., Rasola, A., Forte, M., Lippe, G., The mitochondrial permeability transition pore: channel formation by F-ATP synthase, integration in signal transduction, and role in pathophysiology. Physiol. Rev. 95 (2015), 1111–1155.
7. Cavero, S., Vozza, A., del Arco, A., Palmieri, L., Villa, A., Blanco, E., Runswick, M.J., Walker, J.E., Cerdán, S., Palmieri, F., Satrústegui, J., Identification and metabolic role of the mitochondrial aspartate-glutamate transporter in Saccharomyces cerevisiae. Mol. Microbiol. 50 (2003), 1257–1269.
8. Cavero, S., Traba, J., Del Arco, A., Satrústegui, J., The calcium-dependent ATP-Mg/Pi mitochondrial carrier is a target of glucose-induced calcium signalling in Saccharomyces cerevisiae. Biochem. J. 392 (2005), 537–544.
9. Chen, X.J., Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated with the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae. Genetics 167 (2004), 607–617.
10. 2 + activation kinetics of the two aspartate-glutamate mitochondrial carriers, aralar and citrin: role in the heart malate-aspartate NADH shuttle. J. Biol. Chem. 282 (2007), 7098–7106.
11. Contreras, L., Satrustegui, J., Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways. J. Biol. Chem. 284 (2009), 7091–7099.
12. Contreras, L., Urbieta, A., Kobayashi, K., Saheki, T., Satrústegui, J., Low levels of citrin (SLC25A13) expression in adult mouse brain restricted to neuronal clusters. J. Neurosci. Res. 88 (2010), 1009–1016.
13. del Arco, A., Satrústegui, J., Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain. J. Biol. Chem. 273 (1998), 23327–23334.
14. del Arco, A., Agudo, M., Satrústegui, J., Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues. Biochem. J. 345 (2000), 725–732.
15. del Arco, A., Morcillo, J., Martínez-Morales, J.R., Galián, C., Martos, V., Bovolenta, P., Satrústegui, J., Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues. Eur. J. Biochem. 269 (2002), 3313–3320.
16. del Arco, A., Satrústegui, J., Identification of a novel human subfamily of mitochondrial carriers with calcium-binding domains. J. Biol. Chem. 279 (2004), 24701–24713.
17. del Arco, A., Satrústegui, J., New mitochondrial carriers: an overview. Cell. Mol. Life Sci. 62 (2005), 2204–2227.
18. del Arco, A., Novel variants of human SCaMC-3, an isoform of the ATP-Mg/P(i) mitochondrial carrier, generated by alternative splicing from 3′-flanking transposable elements. Biochem. J. 389 (2005), 647–655.
19. Dimmock, D., Maranda, B., Dionisi-Vici, C., Wang, J., Kleppe, S., Fiermonte, G., Bai, R., Hainline, B., Hamosh, A., O'Brien, W.E., Scaglia, F., Wong, L.J., Citrin deficiency, a perplexing global disorder. Mol. Genet. Metab. 96 (2009), 44–49.
20. Du, J., Cleghorn, W., Contreras, L., Linton, J.D., Chan, G.C., Chertov, A.O., Saheki, T., Govindaraju, V., Sadilek, M., Satrústegui, J., Hurley, J.B., Cytosolic reducing power preserves glutamate in retina. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 18501–18506.
21. Falk, M.J., Li, D., Gai, X., McCormick, E., Place, E., Lasorsa, F.M., Otieno, F.G., Hou, C., Kim, C.E., Abdel-Magid, N., Vazquez, L., Mentch, F.D., Chiavacci, R., Liang, J., Liu, X., Jiang, H., Giannuzzi, G., Marsh, E.D., Yiran, G., Tian, L., Palmieri, F., Hakonarson, H., AGC1 deficiency causes infantile epilepsy, abnormal myelination, and reduced N-acetylaspartate. JIMD Rep. 14 (2014), 77–85.
22. Fiermonte, G., Palmieri, L., Todisco, S., Agrimi, G., Palmieri, F., Walker, J.E., Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J. Biol. Chem. 277 (2002), 19289–19294.
23. Fiermonte, G., De Leonardis, F., Todisco, S., Palmieri, L., Lasorsa, F.M., Palmieri, F., Identification of the mitochondrial ATP-Mg/Pi transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. J. Biol. Chem. 279 (2004), 30722–30730.
24. Fu, H.Y., Zhang, S.R., Wang, X.H., Saheki, T., Kobayashi, K., Wang, J.S., The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia. J. Gastroenterol. 46 (2011), 510–518.
25. 2 + in the nanomolar range regulates glutamate-dependent oxidative phosphorylation on demand. PLoS One, 4, 2009, e8181.
26. 2 + regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle. Biochem. J. 443 (2012), 747–755.
27. Gellerich, F.N., Gizatullina, Z., Gainutdinov, T., Muth, K., Seppet, E., Orynbayeva, Z., Vielhaber, S., The control of brain mitochondrial energization by cytosolic calcium: the mitochondrial gas pedal. IUBMB Life 65 (2013), 180–190.
28. 2 + channels. Mol. Cell 38 (2010), 280–290.
29. 2 +-binding helix-loop-helix EF-hand motifs. Biochem. J. 405 (2007), 199–221.
30. 2 + in the regulation of cellular energetics. Biochemistry 51 (2012), 2959–2973.
31. Gómez-Galán, M., Makarova, J., Llorente-Folch, I., Saheki, T., Pardo, B., Satrústegui, J., Herreras, O., Altered postnatal development of cortico-hippocampal neuronal electric activity in mice deficient for the mitochondrial aspartate-glutamate transporter. J. Cereb. Blood Flow Metab. 32 (2012), 306–317.
32. Harborne, S.P., Ruprecht, J.J., Kunji, E.R., Calcium-induced conformational changes in the regulatory domain of the human mitochondrial ATP-Mg/Pi carrier. Biochim. Biophys. Acta 1847 (2015), 1245–1253.
33. Haynes, R.C. Jr., Picking, R.A., Zaks, W.J., Control of mitochondrial content of adenine nucleotides by submicromolar calcium concentrations and its relationship to hormonal effects. J. Biol. Chem. 261 (1986), 16121–16125.
34. Hoeflich, K.P., Ikura, M., Calmodulin in action: diversity in target recognition and activation mechanisms. Cell 108 (2002), 739–742.
35. Hoffman, N.E., Chandramoorthy, H.C., Shanmughapriya, S., Zhang, X.Q., Vallem, S., Doonan, P.J., Malliankaraman, K., Guo, S., Rajan, S., Elrod, J.W., Koch, W.J., Cheung, J.Y., Madesh, M., SLC25A23 augments mitochondrial Ca²⁺ uptake, interacts with MCU, and induces oxidative stress-mediated cell death. Mol. Biol. Cell 25 (2014), 936–947.
36. Irimia, M., Weatheritt, R.J., Ellis, J.D., Parikshak, N.N., Gonatopoulos-Pournatzis, T., Babor, M., Quesnel-Vallières, M., Tapial, J., Raj, B., O'Hanlon, D., Barrios-Rodiles, M., Sternberg, M.J., Cordes, S.P., Roth, F.P., Wrana, J.L., Geschwind, D.H., Blencowe, B.J., A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell 159 (2014), 1511–1523.
37. Jalil, M.A., Begum, L., Contreras, L., Pardo, B., Iijima, M., Li, M.X., Ramos, M., Marmol, P., Horiuchi, M., Shimotsu, K., Nakagawa, S., Okubo, A., Sameshima, M., Isashiki, Y., Del Arco, A., Kobayashi, K., Satrústegui, J., Saheki, T., Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type mitochondrial aspartate-glutamate carrier. J. Biol. Chem. 280 (2005), 31333–31339.
38. Joyal, J.L., Aprille, J.R., The ATP-Mg/Pi carrier of rat liver mitochondria catalyzes a divalent electroneutral exchange. J. Biol. Chem. 267 (1992), 19198–19203.
39. Kirichok, Y., Krapivinsky, G., Clapham, D.E., The mitochondrial calcium uniporter is a highly selective ion channel. Nature 2004:427 (2004), 360–364.
40. Kobayashi, K., Sinasac, D.S., Iijima, M., Boright, A.P., Begum, L., Lee, J.R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M.A., Kondo, I., Tsui, L.C., Scherer, S.W., Saheki, T., The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat. Genet. 22 (1999), 159–163.
41. Korzeniewski, B., Regulation of oxidative phosphorylation through parallel activation. Biophys. Chem. 129 (2007), 93–110.
42. Kristián, T., Pivovarova, N.B., Fiskum, G., Andrews, S.B., Calcium-induced precipitate formation in brain mitochondria: composition, calcium capacity, and retention. J. Neurochem. 102 (2007), 1346–1356.
43. Kunji, E.R., The role and structure of mitochondrial carriers. FEBS Lett. 564 (2004), 239–244.
44. Kunji, E.R., Crichton, P.G., Mitochondrial carriers function as monomers. Biochim. Biophys. Acta, 1797, 2010 817-731.
45. LaNoue, K.F., Tischler, M.E., Electrogenic characteristics of the mitochondrial glutamate-aspartate antiporter. J. Biol. Chem. 249 (1974), 7522–7528.
46. Lasorsa, F.M., Pinton, P., Palmieri, L., Fiermonte, G., Rizzuto, R., Palmieri, F., Recombinant expression of the Ca(2 +)-sensitive aspartate/glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells. J. Biol. Chem. 278 (2003), 38686–38692.
47. Leverve, X.M., Verhoeven, A.J., Groen, A.K., Meijer, A.J., Tager, J.M., The malate/aspartate shuttle and pyruvate kinase as targets involved in the stimulation of gluconeogenesis by phenylephrine. Eur. J. Biochem. 155 (1986), 551–556.
48. Li, Y.I., Sánchez-Pulido, L., Haerty, W., Ponting, C.P., RBFOX and PTBP1 proteins regulate the alternative splicing of micro-exons in human brain transcripts. Genome Res. 25 (2015), 1–13.
49. Lindsay, K.J., Du, J., Sloat, S.R., Contreras, L., Linton, J.D., Turner, S.J., Sadilek, M., Satrústegui, J., Hurley, J.B., Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 15579–15584.
50. Llorente-Folch, I., Rueda, C.B., Amigo, I., del Arco, A., Saheki, T., Pardo, B., Satrustegui, J., Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons. J. Neurosci. 33 (2013), 13957–13971.
51. Llorente-Folch, I., Rueda, C.B., Pardo, B., Szabadkai, G., Duchen, M.R., Satrustegui, J., The regulation of neuronal mitochondrial metabolism by calcium. J. Physiol. 593 (2015), 3447–3462.
52. Lorenz, A., Lorenz, M., Vothknecht, U.C., Niopek-Witz, S., Neuhaus, H.E., Haferkamp, I., In vitro analyses of mitochondrial ATP/phosphate carriers from Arabidopsis thaliana revealed unexpected Ca(2 +)-effects. BMC Plant Biol., 15, 2015, 238.
53. Maier, H., Wang-Eckhardt, L., Hartmann, D., Gieselmann, V., Eckhardt, M., N-Acetylaspartate synthase deficiency corrects the myelin phenotype in a canavan disease mouse model but does not affect survival time. J. Neurosci. 35 (2015), 14501–14516.
54. 2 + signal transduction in mitochondria from INS-1 clonal beta-cells. J. Biol. Chem. 284 (2009), 515–524.
55. 2 +-dependent solute carrier in the liver identified by mRNA differential display. J. Biol. Chem. 278 (2003), 9520–9527.
56. McCormack, J.G., Halestrap, A.P., Denton, R.M., Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol. Rev. 70 (1990), 391–425.
57. Monné, M., Miniero, D.V., Obata, T., Daddabbo, L., Palmieri, L., Vozza, A., Nicolardi, M.C., Fernie, A.R., Palmieri, F., Functional characterization and organ distribution of three mitochondrial ATP-Mg/Pi carriers in Arabidopsis thaliana. Biochim. Biophys. Acta 1847 (2015), 1220–1230.
58. Napolioni, V., Persico, A.M., Porcelli, V., Palmieri, L., The mitochondrial aspartate/glutamate carrier AGC1 and calcium homeostasis: physiological links and abnormalities in autism. Mol. Neurobiol. 44 (2011), 83–92.
59. Nicholls, D.G., Chalmers, S., The integration of mitochondrial calcium transport and storage. J. Bioenerg. Biomembr. 36 (2004), 277–281.
60. Nosek, M.T., Dransfield, D.T., Aprille, J.R., Calcium stimulates ATP-Mg/Pi carrier activity in rat liver mitochondria. J. Biol. Chem. 265 (1990), 8444–8450.
61. Nury, H., Dahout-Gonzalez, C., Trézéguet, V., Lauquin, G.J., Brandolin, G., Pebay-Peyroula, E., Relations between structure and function of the mitochondrial ADP/ATP carrier. Annu. Rev. Biochem. 75 (2006), 713–741.
62. Palmieri, L., Pardo, B., Lasorsa, F.M., del Arco, A., Kobayashi, K., Iijima, M., Runswick, M.J., Walker, J.E., Saheki, T., Satrústegui, J., Palmieri, F., Citrin and aralar1 are Ca(2 +)-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 20 (2001), 5060–5069.
63. Palmieri, F., The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch. 447 (2004), 689–709.
64. Palmieri, F., The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol. Asp. Med. 34 (2013), 465–484.
65. Palmieri, F., Monné, M., Discoveries, metabolic roles and diseases of mitochondrial carriers: a review. Biochim. Biophys. Acta 1863 (2016), 2362–2378.
66. 2 + signals to neuronal mitochondria. J. Biol. Chem. 281 (2006), 1039–1047.
67. Pardo, B., Rodrigues, T.B., Contreras, L., Garzón, M., Llorente-Folch, I., Kobayashi, K., Saheki, T., Cerdan, S., Satrústegui, J., Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation. J. Cereb. Blood Flow Metab. 31 (2011), 90–101.
68. Pebay-Peyroula, E., Dahout-Gonzalez, C., Kahn, R., Trézéguet, V., Lauquin, G.J., Brandolin, G., Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 426 (2003), 39–44.
69. 2 +-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord. Brain Res. Dev. Brain Res. 143 (2003), 33–46.
70. Ramos, M., del Arco, A., Pardo, B., Martínez-Serrano, A., Martínez-Morales, J.R., Kobayashi, K., Yasuda, T., Bogónez, E., Bovolenta, P., Saheki, T., Satrústegui, J., Ramos, M., Pardo, B., Llorente-Folch, I., Saheki, T., del Arco, A., Satrústegui, J., Deficiency of the mitochondrial transporter of aspartate/glutamate aralar/AGC1 causes hypomyelination and neuronal defects unrelated to myelin deficits in mouse brain. J. Neurosci. Res. 89 (2011), 2008–2017.
71. Robinson, A.J., Kunji, E.R., Mitochondrial carriers in the cytoplasmic state have a common substrate binding site. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 2617–2622.
72. Robinson, A.J., Overy, C., Kunji, E.R.S., The mechanism of transport by mitochondrial carriers based on analysis of symmetry. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 17766–17771.
73. Rubi, B., del Arco, A., Bartley, C., Satrustegui, J., Maechler, P., The malate-aspartate NADH shuttle member Aralar1 determines glucose metabolic fate, mitochondrial activity, and insulin secretion in beta cells. J. Biol. Chem. 279 (2004), 55659–55666.
74. Rueda, C.B., Llorente-Folch, I., Amigo, I., Contreras, L., González-Sánchez, P., Martínez-Valero, P., Juaristi, I., Pardo, B., del Arco, A., Satrústegui, J., Ca(2 +) regulation of mitochondrial function in neurons. Biochim. Biophys. Acta 1837 (2014), 1617–1624.
75. Rueda, C.B., Traba, J., Amigo, I., Llorente-Folch, I., González-Sánchez, P., Pardo, B., Esteban, J.A., del Arco, A., Satrústegui, J., Mitochondrial ATP-Mg/Pi carrier SCaMC-3/Slc25a23 counteracts PARP-1-dependent fall in mitochondrial ATP caused by excitotoxic insults in neurons. J. Neurosci. 35 (2015), 3566–3581.
76. Run, C., Yang, Q., Liu, Z., OuYang, B., Chou, J.J., Molecular basis of MgATP selectivity of the mitochondrial SCaMC carrier. Structure 23 (2015), 1394–1403.
77. Saheki, T., Kobayashi, K., Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J. Hum. Genet. 47 (2002), 333–341.
78. Saheki, T., Iijima, M., Li, M.X., Kobayashi, K., Horiuchi, M., Ushikai, M., Okumura, F., Meng, X.J., Inoue, I., Tajima, A., Moriyama, M., Eto, K., Kadowaki, T., Sinasac, D.S., Tsui, L.C., Tsuji, M., Okano, A., Kobayashi, T., Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency. J. Biol. Chem. 282 (2007), 25041–25052.
79. Saheki, T., Inoue, K., Ono, H., Tushima, A., Katsura, N., Yokogawa, M., Yoshidumi, Y., Kuhara, T., Ohse, M., Eto, K., Kadowaki, T., Sinasac, D.S., Kobayashi, K., Metabolomic analysis reveals hepatic metabolite perturbations in citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mice, a model of human citrin deficiency. Mol. Genet. Metab. 104 (2011), 492–500.
80. Sakurai, T., Ramoz, N., Barreto, M., Gazdoiu, M., Takahashi, N., Gertner, M., Dorr, N., Gama Sosa, M.A., De Gasperi, R., Perez, G., Schmeidler, J., Mitropoulou, V., Le, H.C., Lupu, M., Hof, P.R., Elder, G.A., Buxbaum, J.D., Slc25a12 disruption alters myelination and neurofilaments: a model for a hypomyelination syndrome and childhood neurodevelopmental disorders. Biol. Psychiatry 67 (2010), 887–894.
81. Saraste, M., Walker, J.E., Internal sequence repeats and the path of polypeptide in mitochondrial ADP/ATP translocase. FEBS Lett. 144 (1982), 250–254.
82. Satrústegui, J., Pardo, B., del Arco, A., Mitochondrial transporters as novel targets for intracellular calcium signaling. Physiol. Rev. 87 (2007), 29–67.
83. Satrústegui, J., Contreras, L., Ramos, M., Mármol, P., del Arco, A., Saheki, T., Pardo, B., Role of aralar, the mitochondrial transporter of aspartate-glutamate, in brain N-acetylaspartate formation and Ca(2 +) signaling in neuronal mitochondria. J. Neurosci. Res. 85 (2007), 3359–3366.
84. Satrústegui, J., Bak, L.K., Fluctuations in cytosolic calcium regulate the neuronal malate-aspartate NADH shuttle: implications for neuronal energy metabolism. Neurochem. Res. 40 (2015), 2425–2430.
85. Song, Y.Z., Zhang, Z.H., Lin, W.X., Zhao, X.J., Deng, M., Ma, Y.L., Guo, L., Chen, F.P., Long, X.L., He, X.L., Sunada, Y., Soneda, S., Nakatomi, A., Dateki, S., Ngu, L.H., Kobayashi, K., Saheki, T., SLC25A13 gene analysis in citrin deficiency: sixteen novel mutations in East Asian patients, and the mutation distribution in a large pediatric cohort in China. PLoS One, 8, 2013, e74544.
86. Stael, S., Rocha, A.G., Robinson, A.J., Kmiecik, P., Vothknecht, U.C., Teige, M., Arabidopsis calcium-binding mitochondrial carrier proteins as potential facilitators of mitochondrial ATP-import and plastid SAM-import. FEBS Lett. 585 (2011), 3935–3940.
87. Thangaratnarajah, C., Ruprecht, J.J., Kunji, E.R., Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. Nat. Commun., 5, 2014, 5491.
88. Traba, J., Froschauer, E.M., Wiesenberger, G., Satrústegui, J., del Arco, A., Yeast mitochondria import ATP through the calcium-dependent ATP-Mg/Pi carrier Sal1p, and are ATP consumers during aerobic growth in glucose. Mol. Microbiol. 69 (2008), 570–585.
89. Traba, J., Satrústegui, J., del Arco, A., Characterization of SCaMC-3-like/slc25a41, a novel calcium-independent mitochondrial ATP-Mg/Pi carrier. Biochem. J. 418 (2009), 125–133.
90. 2 + buffering. Cell Death Differ. 19 (2012), 650–660.
91. Urano, T., Shiraki, M., Sasaki, N., Ouchi, Y., Inoue, S., SLC25A24 as a novel susceptibility gene for low fat mass in humans and mice. J. Clin. Endocrinol. Metab. 100 (2015), E655–E663.
92. 2 +-dependent member of the mitochondrial carrier superfamily. Proc. Natl. Acad. Sci. U. S. A. 94 (1997), 8509–8514.
93. Wibom, R., Lasorsa, F.M., Töhönen, V., Barbaro, M., Sterky, F.H., Kucinski, T., Naess, K., Jonsson, M., Pierri, C.L., Palmieri, F., Wedell, A., AGC1 deficiency associated with global cerebral hypomyelination. N. Engl. J. Med. 361 (2009), 489–495.
94. Wongkittichote, P., Tungpradabkul, S., Wattanasirichaigoon, D., Jensen, L.T., Prediction of the functional effect of novel SLC25A13 variants using a S. cerevisiae model of AGC2 deficiency. J. Inherit. Metab. Dis. 36 (2013), 821–830.
95. Yang, Q., Brüschweiler, S., Chou, J.J., A self-sequestered calmodulin-like Ca²⁺ sensor of mitochondrial SCaMC carrier and its implication to Ca²⁺-dependent ATP-Mg/P(i) transport. Structure 22 (2014), 209–217.