Computational studies of the mitochondrial carrier family SLC25. Present status and future perspectives

References

1. Palmieri, F. Mitochondrial transporters of the SLC25 family and associated diseases: a review. J Inherit Metab Dis 2014;37:565–75. https://doi.org/10.1007/s10545-014-9708-5.Search in Google Scholar

2. Claeys, D, Azzi, A. Tricarboxylate carrier of bovine liver mitochondria. Purification and reconstitution. J Biol Chem 1989;264:14627–30. https://doi.org/10.1016/S0021-9258(18)63743-3.Search in Google Scholar

3. Pebay-Peyroula, E, Dahout-Gonzalez, C, Kahn, R, Trézéguet, V, Lauquin, GJM, Brandolin, G. Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 2003;426:39–44. https://doi.org/10.1038/nature02056.Search in Google Scholar

4. Palmieri, F, Stipani, I, Quagliariello, E, Klingenberg, M. Kinetic study of the tricarboxylate carrier in rat liver mitochondria. Eur J Biochem 1972;26:587–94. https://doi.org/10.1111/j.1432-1033.1972.tb01801.x.Search in Google Scholar

5. Majd, H, King, MS, Smith, AC, Kunji, ERS. Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis. Biochim Biophys Acta Bioenerg 2018;1859:1–7. https://doi.org/10.1016/j.bbabio.2017.10.002.Search in Google Scholar

6. Porcelli, V, Longo, A, Palmieri, L, Closs, EI, Palmieri, F. Asymmetric dimethylarginine is transported by the mitochondrial carrier SLC25A2. Amino Acids 2016;48:427–36. https://doi.org/10.1007/s00726-015-2096-9.Search in Google Scholar

7. Stappen, R, Krämer, R. Kinetic mechanism of phosphate/phosphate and phosphate/OH-antiports catalyzed by reconstituted phosphate carrier from beef heart mitochondria. J Biol Chem 1994;269:11240–6. https://doi.org/10.1016/s0021-9258(19)78116-2.Search in Google Scholar

8. Boulet, A, Vest, KE, Maynard, MK, Gammon, MG, Russell, AC, Mathews, AT, et al.. The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. J Biol Chem 2018;293:1887–96. https://doi.org/10.1074/jbc.RA117.000265.Search in Google Scholar PubMed PubMed Central

9. Bertholet, AM, Chouchani, ET, Kazak, L, Angelin, A, Fedorenko, A, Long, JZ, et al.. H+ transport is an integral function of the mitochondrial ADP/ATP carrier. Nature 2019;571:515–20. https://doi.org/10.1038/s41586-019-1400-3.Search in Google Scholar PubMed PubMed Central

10. Klingenberg, M. The ADP and ATP transport in mitochondria and its carrier. Biochim Biophys Acta Biomembr 2008;1778:1978–2021. https://doi.org/10.1016/j.bbamem.2008.04.011.Search in Google Scholar PubMed

11. Stepien, G, Torroni, A, Chung, AB, Hodge, JA, Wallaces, DC. Differential expression of adenine nucleotide translocator isoforms in mammalian tissues and during muscle cell differentiation. J Biol Chem 1992;267:14592–7. https://doi.org/10.1016/s0021-9258(18)42082-0.Search in Google Scholar

12. Casteilla, L, Blondel, O, Klaus, S, Raimbault, S, Diolez, P, Moreau, F, et al.. Stable expression of functional mitochondrial uncoupling protein in Chinese hamster ovary cells. Proc Natl Acad Sci USA 1990;87. https://doi.org/10.1073/pnas.87.13.5124.https://doi.org/10.1073/pnas.87.13.5124Search in Google Scholar

13. Berardi, MJ, Chou, JJ. Fatty acid flippase activity of UCP2 is essential for its proton transport in mitochondria. Cell Metabol 2014;20:541–52. https://doi.org/10.1016/j.cmet.2014.07.004.Search in Google Scholar

14. Vozza, A, Parisi, G, De Leonardis, F, Lasorsa, FM, Castegna, A, Amorese, D, et al.. UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci USA 2014;111:960–5. https://doi.org/10.1073/pnas.1317400111.Search in Google Scholar

15. Macher, G, Koehler, M, Rupprecht, A, Kreiter, J, Hinterdorfer, P, Pohl, EE. Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and phosphate. Biochim Biophys Acta Biomembr 2018;1860:664–72. https://doi.org/10.1016/j.bbamem.2017.12.001.Search in Google Scholar

16. Palmieri, F, Prezioso, G, Quagliariello, E, Klingenberg, M. Kinetic study of the dicarboxylate carrier in rat liver mitochondria. Eur J Biochem 1971;22:66–74. https://doi.org/10.1111/j.1432-1033.1971.tb01515.x.Search in Google Scholar

17. Crompton, M, Palmieri, F, Capano, M, Quagliariello, E. The transport of thiosulphate in rat liver mitochondria. FEBS Lett 1974;46:247–50. https://doi.org/10.1016/0014-5793(74)80379-0.Search in Google Scholar

18. Chen, Z, Lash, LH. Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers. J Pharmacol Exp Therapeut 1998;285:608–18.Search in Google Scholar

19. Palmieri, F, Quagliariello, E, Klingenberg, M. Kinetics and specificity of the oxoglutarate carrier in rat-liver mitochondria. Eur J Biochem 1972;29:408–16. https://doi.org/10.1111/j.1432-1033.1972.tb02003.x.Search in Google Scholar

20. Passarella, S, Palmieri, F, Quagliariello, E. The transport of oxaloacetate in isolated mitochondria. Arch Biochem Biophys 1977;180:160–8. https://doi.org/10.1016/0003-9861(77)90020-0.Search in Google Scholar

21. LaNoue, KF, Tischler, ME. Electrogenic characteristics of the mitochondrial glutamate aspartate antiporter. J Biol Chem 1974;249:7522–8. https://doi.org/10.1016/s0021-9258(19)81269-3.Search in Google Scholar

22. Palmieri, L, Pardo, B, Lasorsa, FM, Del Arco, A, Kobayashi, K, Iijima, M, et al.. Citrin and aralar1 are Ca2+-stimulated aspartate/glutamate transporters in mitochondria. EMBO J 2001;20:5060–9. https://doi.org/10.1093/emboj/20.18.5060.Search in Google Scholar PubMed PubMed Central

23. Gorgoglione, R, Porcelli, V, Santoro, A, Daddabbo, L, Vozza, A, Monné, M, et al.. The human uncoupling proteins 5 and 6 (UCP5/SLC25A14 and UCP6/SLC25A30) transport sulfur oxyanions, phosphate and dicarboxylates. Biochim Biophys Acta Bioenerg 2019;1860:724–33. https://doi.org/10.1016/j.bbabio.2019.07.010.Search in Google Scholar PubMed

24. Fiermonte, G, Dolce, V, David, L, Santorelli, FM, Dionisi-Vici, C, Palmieri, F, et al.. The mitochondrial ornithine transporter: bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem 2003;278:32778–83. https://doi.org/10.1074/jbc.M302317200.Search in Google Scholar PubMed

25. Agrimi, G, Russo, A, Scarcia, P, Palmieri, F. The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+. Biochem J 2012;443:241–7. https://doi.org/10.1042/BJ20111420.Search in Google Scholar PubMed

26. Fiermonte, G, Palmieri, L, Todisco, S, Agrimi, G, Palmieri, F, Walker, JE. Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem 2002;277:19289–94. https://doi.org/10.1074/jbc.M201572200.Search in Google Scholar PubMed

27. Kang, J, Samuels, DC. The evidence that the DNC (SLC25A19) is not the mitochondrial deoxyribonucleotide carrier. Mitochondrion 2008;8:103–8. https://doi.org/10.1016/j.mito.2008.01.001.Search in Google Scholar PubMed

28. Indiveri, C, Iacobazzi, V, Giangregorio, N, Palmieri, F. Bacterial overexpression, purification, and reconstitution of the carnitine/acylcarnitine carrier from rat liver mitochondria. Biochem Biophys Res Commun 1998;249:589–94. https://doi.org/10.1006/bbrc.1998.9197.Search in Google Scholar PubMed

29. Fiermonte, G, Dolce, V, Palmieri, L, Ventura, M, Runswick, MJ, Palmieri, F, et al.. Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location. J Biol Chem 2001;276:8225–30. https://doi.org/10.1074/jbc.M009607200.Search in Google Scholar PubMed

30. Fiermonte, G, De Leonardis, F, Todisco, S, Palmieri, L, Lasorsa, FM, Palmieri, F. Identification of the mitochondrial ATP-Mg/Pi transporter: bacterial expression, reconstitution, functional characterization, and tissue distribution. J Biol Chem 2004;279:30722–30. https://doi.org/10.1074/jbc.M400445200.Search in Google Scholar PubMed

31. Agrimi, G, Di Noia, MA, Marobbio, CMT, Fiermonte, G, Lasorsa, FM, Palmieri, F. Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. Bio chem J 2004;379:183–90. https://doi.org/10.1042/BJ20031664.Search in Google Scholar PubMed PubMed Central

32. Hoang, T, Smith, MD, Jelokhani-Niaraki, M. Toward understanding the mechanism of ion transport activity of neuronal uncoupling proteins UCP2, UCP4, and UCP5. Biochemistry 2012;51:4004–14. https://doi.org/10.1021/bi3003378.Search in Google Scholar PubMed

33. Paradkar, PN, Zumbrennen, KB, Paw, BH, Ward, DM, Kaplan, J. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol Cell Biol 2009;29:1007–16. https://doi.org/10.1128/mcb.01685-08.Search in Google Scholar PubMed PubMed Central

34. Porcelli, V, Fiermonte, G, Longo, A, Palmieri, F. The human gene SLC25A29, of solute carrier family 25, encodes a mitochondrial transporter of basic amino acids. J Biol Chem 2014;289:13374–84. https://doi.org/10.1074/jbc.M114.547448.Search in Google Scholar PubMed PubMed Central

35. Dolce, V, Scarcia, P, Iacopetta, D, Palmieri, F. A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Lett 2005;579:633–7. https://doi.org/10.1016/j.febslet.2004.12.034.Search in Google Scholar PubMed

36. McCarthy, EA, Titus, SA, Taylor, SM, Jackson-Cook, C, Moran, RG. A mutation inactivating the mitochondrial inner membrane folate transporter creates a glycine requirement for survival of Chinese hamster cells. J Biol Chem 2004;279:33829–36. https://doi.org/10.1074/jbc.M403677200.Search in Google Scholar PubMed

37. Titus, SA, Moran, RG. Retrovirally mediated complementation of the glyB phenotype. Cloning of a human gene encoding the carrier for entry of folates into mitochondria. J Biol Chem 2000;275:36811–7. https://doi.org/10.1074/jbc.M005163200.Search in Google Scholar PubMed

38. Di Noia, MA, Todisco, S, Cirigliano, A, Rinaldi, T, Agrimi, G, Iacobazzi, V, et al.. The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode two mitochondrial pyrimidine nucleotide transporters. J Biol Chem 2014;289:33137–48. https://doi.org/10.1074/jbc.M114.610808.Search in Google Scholar PubMed PubMed Central

39. Lunetti, P, Damiano, F, De Benedetto, G, Siculella, L, Pennetta, A, Muto, L, et al.. Characterization of human and yeast mitochondrial glycine carriers with implications for heme biosynthesis and anemia. J Biol Chem 2016;291:19746–59. https://doi.org/10.1074/jbc.M116.736876.Search in Google Scholar PubMed PubMed Central

40. Traba, J, Satrústegui, J, del Arco, A. Characterization of SCaMC-3-like/slc25a41, a novel calcium-independent mitochondrial ATP-Mg/Pi carrier. Biochem J 2009;418:125–33. https://doi.org/10.1042/BJ20081262.Search in Google Scholar PubMed

41. Fiermonte, G, Paradies, E, Todisco, S, Marobbio, CMT, Palmieri, F. A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3′,5′-diphosphate in human mitochondria. J Biol Chem 2009;284:18152–9. https://doi.org/10.1074/jbc.M109.014118.Search in Google Scholar PubMed PubMed Central

42. Yoneshiro, T, Wang, Q, Tajima, K, Matsushita, M, Maki, H, Igarashi, K, et al.. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature 2019;572:614–9. https://doi.org/10.1038/s41586-019-1503-x.Search in Google Scholar PubMed PubMed Central

43. Jin, X, Yang, YD, Chen, K, Lv, ZY, Zheng, L, Liu, YP, et al.. HDMCP uncouples yeast mitochondrial respiration and alleviates steatosis in L02 and hepG2 cells by decreasing ATP and H2O2 levels: a novel mechanism for NAFLD. J Hepatol 2009;50:1019–28. https://doi.org/10.1016/j.jhep.2008.10.034.Search in Google Scholar PubMed

44. Luongo, TS, Eller, JM, Lu, MJ, Niere, M, Raith, F, Perry, C, et al.. SLC25A51 is a mammalian mitochondrial NAD+ transporter. Nature 2020;588:174–9. https://doi.org/10.1038/s41586-020-2741-7.Search in Google Scholar PubMed PubMed Central

45. Robinson, AJ, Overy, C, Kunji, ERS. The mechanism of transport by mitochondrial carriers based on analysis of symmetry. Proc Natl Acad Sci USA 2008;105:17766–71. https://doi.org/10.1073/pnas.0809580105.Search in Google Scholar PubMed PubMed Central

46. Palmieri, F, Scarcia, P, Monné, M. Diseases caused by mutations in mitochondrial carrier genes SLC25: a review. Biomolecules 2020;10:655. https://doi.org/10.3390/biom10040655.Search in Google Scholar PubMed PubMed Central

47. Palmieri, F, Monné, M. Discoveries, metabolic roles and diseases of mitochondrial carriers: a review. Biochim Biophys Acta Mol Cell Res 2016;1863:2362–78. https://doi.org/10.1016/j.bbamcr.2016.03.007.Search in Google Scholar PubMed

48. Tsirigos, KD, Peters, C, Shu, N, Käll, L, Elofsson, A. The TOPCONS web server for consensus prediction of membrane protein topology and signal peptides. Nucleic Acids Res 2015;43:W401–7. https://doi.org/10.1093/nar/gkv485.Search in Google Scholar PubMed PubMed Central

49. Webb, B, Sali, A. Comparative protein structure modeling using MODELLER. Curr Protoc Bioinf 2016;54. 5.6.1–37 https://doi.org/10.1002/cpbi.3.Search in Google Scholar PubMed PubMed Central

50. Croll, TI, Sammito, MD, Kryshtafovych, A, Read, RJ. Evaluation of template‐based modeling in CASP13. Proteins Struct Funct Bioinf 2019;87:1113–27. https://doi.org/10.1002/prot.25800.Search in Google Scholar PubMed PubMed Central

51. Baker, D, Sali, A. Protein structure prediction and structural genomics. Science 2001;294:93–6. https://doi.org/10.1126/science.1065659.Search in Google Scholar PubMed

52. Abriata, LA, Tamò, GE, Monastyrskyy, B, Kryshtafovych, A, Dal Peraro, M. Assessment of hard target modeling in CASP12 reveals an emerging role of alignment-based contact prediction methods. Proteins Struct Funct Bioinf 2018;86:97–112. https://doi.org/10.1002/prot.25423.Search in Google Scholar

53. Yang, J, Zhang, Y. I-TASSER server: new development for protein structure and function predictions. Nucleic Acids Res 2015;43:W174–81. https://doi.org/10.1093/nar/gkv342.Search in Google Scholar

54. Karplus, M, McCammon, JA. Molecular dynamics simulations of biomolecules. Nat Struct Biol 2002;9:646–52. https://doi.org/10.1038/nsb0902-646.Search in Google Scholar

55. Wu, EL, Cheng, X, Jo, S, Rui, H, Song, KC, Dávila-Contreras, EM, et al.. CHARMM-GUI membrane builder toward realistic biological membrane simulations. J Comput Chem 2014;35:1997–2004. https://doi.org/10.1002/jcc.23702.Search in Google Scholar

56. Kandt, C, Ash, WL, Peter Tieleman, D. Setting up and running molecular dynamics simulations of membrane proteins. Methods 2007;41:475–88. https://doi.org/10.1016/j.ymeth.2006.08.006.Search in Google Scholar

57. Jefferies, D, Khalid, S. Atomistic and coarse-grained simulations of membrane proteins: a practical guide. Methods 2020;185:15–27. https://doi.org/10.1016/j.ymeth.2020.02.007.Search in Google Scholar

58. Sugita, Y, Okamoto, Y. Replica-exchange molecular dynamics method for protein folding. Chem Phys Lett 1999;314:141–51. https://doi.org/10.1016/S0009-2614(99)01123-9.Search in Google Scholar

59. Seeliger, D, de Groot, BL. Protein thermostability calculations using alchemical free energy simulations. Bio phys J 2010;98:2309–16. https://doi.org/10.1016/j.bpj.2010.01.051.Search in Google Scholar PubMed PubMed Central

60. Laio, A, Parrinello, M. Escaping free-energy minima. Proc Natl Acad Sci USA 2002;99:12562–6. https://doi.org/10.1073/pnas.202427399.Search in Google Scholar PubMed PubMed Central

61. Darve, E, Rodríguez-Gómez, D, Pohorille, A. Adaptive biasing force method for scalar and vector free energy calculations. J Chem Phys 2008;128:144120. https://doi.org/10.1063/1.2829861.Search in Google Scholar PubMed

62. Harpole, TJ, Delemotte, L. Conformational landscapes of membrane proteins delineated by enhanced sampling molecular dynamics simulations. Biochim Biophys Acta Biomembr 2018;1860:909–26. https://doi.org/10.1016/j.bbamem.2017.10.033.Search in Google Scholar PubMed

63. Robinson, AJ, Kunji, ERS. Mitochondrial carriers in the cytoplasmic state have a common substrate binding site. Proc Natl Acad Sci USA 2006;103:2617–22. https://doi.org/10.1073/pnas.0509994103.Search in Google Scholar PubMed PubMed Central

64. Kunji, ERS, Robinson, AJ. The conserved substrate binding site of mitochondrial carriers. Biochim Biophys Acta Bioenerg 2006;1757:1237–48. https://doi.org/10.1016/j.bbabio.2006.03.021.Search in Google Scholar PubMed

65. Falconi, M, Chillemi, G, Di Marino, D, D’Annessa, I, Morozzo della Rocca, B, Palmieri, L, et al.. Structural dynamics of the mitochondrial ADP/ATP carrier revealed by molecular dynamics simulation studies. Proteins Struct Funct Bioinf 2006;65:681–91. https://doi.org/10.1002/prot.21102.Search in Google Scholar PubMed

66. Wang, Y, Tajkhorshid, E. Electrostatic funneling of substrate in mitochondrial inner membrane carriers. Proc Natl Acad Sci USA 2008;105:9598–603. https://doi.org/10.1073/pnas.0801786105.Search in Google Scholar PubMed PubMed Central

67. Dehez, F, Pebay-Peyroula, E, Chipot, C. Binding of ADP in the mitochondrial ADP/ATP carrier is driven by an electrostatic funnel. J Am Chem Soc 2008;130:12725–33. https://doi.org/10.1021/ja8033087.Search in Google Scholar PubMed

68. Pietropaolo, A, Pierri, CL, Palmieri, F, Klingenberg, M. The switching mechanism of the mitochondrial ADP/ATP carrier explored by free-energy landscapes. Biochim Biophys Acta Bioenerg 2016;1857:772–81. https://doi.org/10.1016/j.bbabio.2016.02.006.Search in Google Scholar PubMed

69. Barducci, A, Bussi, G, Parrinello, M. Well-tempered metadynamics: a smoothly converging and tunable free-energy method. Phys Rev Lett 2008;100:020603. https://doi.org/10.1103/PhysRevLett.100.020603.Search in Google Scholar PubMed

70. Raiteri, P, Laio, A, Gervasio, FL, Micheletti, C, Parrinello, M. Efficient reconstruction of complex free energy landscapes by multiple walkers metadynamics. J Phys Chem B 2006;110:3533–9. https://doi.org/10.1021/jp054359r.Search in Google Scholar PubMed

71. Prinz, JH, Wu, H, Sarich, M, Keller, B, Senne, M, Held, M, et al.. Markov models of molecular kinetics: generation and validation. J Chem Phys 2011;134:174105. https://doi.org/10.1063/1.3565032.Search in Google Scholar PubMed

72. Springett, R, King, MS, Crichton, PG, Kunji, ERS. Modelling the free energy profile of the mitochondrial ADP/ATP carrier. Biochim Biophys Acta Bioenerg 2017;1858:906–14. https://doi.org/10.1016/j.bbabio.2017.05.006.Search in Google Scholar PubMed PubMed Central

73. Tamura, K, Hayashi, S. Atomistic modeling of alternating access of a mitochondrial ADP/ATP membrane transporter with molecular simulations. PloS One 2017;12:e0181489. https://doi.org/10.1371/journal.pone.0181489.Search in Google Scholar PubMed PubMed Central

74. Tamura, K, Hayashi, S. Linear response path following: a molecular dynamics method to simulate global conformational changes of protein upon ligand binding. J Chem Theor Comput 2015;11:2900–17. https://doi.org/10.1021/acs.jctc.5b00120.Search in Google Scholar PubMed

75. Yi, Q, Li, Q, Yao, S, Chen, Y, Guan, MX, Cang, X. Molecular dynamics simulations on apo ADP/ATP carrier shed new lights on the featured motif of the mitochondrial carriers. Mitochondrion 2019;47:94–102. https://doi.org/10.1016/j.mito.2019.05.006.Search in Google Scholar PubMed

76. Horvath, SE, Daum, G. Lipids of mitochondria. Prog Lipid Res 2013;52:590–614. https://doi.org/10.1016/j.plipres.2013.07.002.Search in Google Scholar PubMed

77. Beyer, K, Klingenberg, M. ADP/ATP carrier protein from beef heart mitochondria has high amounts of tightly bound cardiolipin, as revealed by 31P nuclear magnetic resonance. Biochemistry 1985;24:3821–6. https://doi.org/10.1021/bi00336a001.Search in Google Scholar PubMed

78. Klingenberg, M. Cardiolipin and mitochondrial carriers. Biochim Biophys Acta Biomembr 2009;1788:2048–58. https://doi.org/10.1016/j.bbamem.2009.06.007.Search in Google Scholar PubMed

79. Ruprecht, JJ, Hellawell, AM, Harding, M, Crichton, PG, McCoy, AJ, Kunji, ERS. Structures of yeast mitochondrial ADP/ATP carriers support a domain-based alternating-access transport mechanism. Proc Natl Acad Sci USA 2014;111:E426–34. https://doi.org/10.1073/pnas.1320692111.Search in Google Scholar PubMed PubMed Central

80. Berardi, MJ, Shih, WM, Harrison, SC, Chou, JJ. Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching. Nature 2011;476:109–14. https://doi.org/10.1038/nature10257.Search in Google Scholar PubMed PubMed Central

81. Hedger, G, Rouse, SL, Domański, J, Chavent, M, Koldsø, H, Sansom, MSP. Lipid-loving ANTs: molecular simulations of cardiolipin interactions and the organization of the adenine nucleotide translocase in model mitochondrial membranes. Biochemistry 2016;55:6238–49. https://doi.org/10.1021/acs.biochem.6b00751.Search in Google Scholar PubMed PubMed Central

82. Nury, H, Dahout-Gonzalez, C, Trézéguet, V, Lauquin, G, Brandolin, G, Pebay-Peyroula, E. Structural basis for lipid-mediated interactions between mitochondrial ADP/ATP carrier monomers. FEBS Lett 2005;579:6031–6. https://doi.org/10.1016/j.febslet.2005.09.061.Search in Google Scholar PubMed

83. Duncan, AL, Ruprecht, JJ, Kunji, ERS, Robinson, AJ. Cardiolipin dynamics and binding to conserved residues in the mitochondrial ADP/ATP carrier. Biochim Biophys Acta Biomembr 2018;1860:1035–45. https://doi.org/10.1016/j.bbamem.2018.01.017.Search in Google Scholar PubMed PubMed Central

84. Mao, X, Yao, S, Yi, Q, Xu, ZM, Cang, X. Function-related asymmetry of the specific cardiolipin binding sites on the mitochondrial ADP/ATP carrier. Biochim Biophys Acta Biomembr 2021;1863:183466 https://doi.org/10.1016/j.bbamem.2020.183466.Search in Google Scholar PubMed

85. Ruprecht, JJ, King, MS, Zögg, T, Aleksandrova, AA, Pardon, E, Crichton, PG, et al.. The molecular mechanism of transport by the mitochondrial ADP/ATP carrier. Cell 2019;176:435–47.e15. https://doi.org/10.1016/j.cell.2018.11.025.Search in Google Scholar PubMed PubMed Central

86. Škulj, S, Brkljača, Z, Vazdar, M. Molecular dynamics simulations of the elusive matrix‐open state of mitochondrial ADP/ATP carrier. Isr J Chem 2020;60:735–43. https://doi.org/10.1002/ijch.202000011.Search in Google Scholar

87. Abriata, LA, Tamò, GE, Dal Peraro, M. A further leap of improvement in tertiary structure prediction in CASP13 prompts new routes for future assessments. Proteins Struct Funct Bioinf 2019;87:1100–12. https://doi.org/10.1002/prot.25787.Search in Google Scholar PubMed

88. Senior, AW, Evans, R, Jumper, J, Kirkpatrick, J, Sifre, L, Green, T, et al.. Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13). Proteins Struct Funct Bioinf 2019;87:1141–8. https://doi.org/10.1002/prot.25834.Search in Google Scholar PubMed PubMed Central

89. Senior, AW, Evans, R, Jumper, J, Kirkpatrick, J, Sifre, L, Green, T, et al.. Improved protein structure prediction using potentials from deep learning. Nature 2020;577:706–10. https://doi.org/10.1038/s41586-019-1923-7.Search in Google Scholar PubMed

90. Xu, J. Distance-based protein folding powered by deep learning. Proc Natl Acad Sci USA 2019;116:16856–65. https://doi.org/10.1073/pnas.1821309116.Search in Google Scholar PubMed PubMed Central

91. Yang, J, Anishchenko, I, Park, H, Peng, Z, Ovchinnikov, S, Baker, D. Improved protein structure prediction using predicted interresidue orientations. Proc Natl Acad Sci USA 2020;117:1496–503. https://doi.org/10.1073/pnas.1914677117.Search in Google Scholar PubMed PubMed Central

92. Bonomi, M, Bussi, G, Camilloni, C, Tribello, GA, Banáš, P, Barducci, A, et al.. Promoting transparency and reproducibility in enhanced molecular simulations. Nat Methods 2019;16:670–3. https://doi.org/10.1038/s41592-019-0506-8.Search in Google Scholar

93. Tribello, GA, Bonomi, M, Branduardi, D, Camilloni, C, Bussi, G. PLUMED 2: new feathers for an old bird. Comput Phys Commun 2014;185:604–13. https://doi.org/10.1016/j.cpc.2013.09.018.Search in Google Scholar

94. Heo, L, Feig, M. Experimental accuracy in protein structure refinement via molecular dynamics simulations. Proc Natl Acad Sci USA 2018;115:13276–81. https://doi.org/10.1073/pnas.1811364115.Search in Google Scholar

95. Dutagaci, B, Heo, L, Feig, M. Structure refinement of membrane proteins via molecular dynamics simulations. Proteins Struct Funct Bioinf 2018;86:738–50. https://doi.org/10.1002/prot.25508.Search in Google Scholar

96. Krebs, JJR, Hauser, H, Carafoli, E. Asymmetric distribution of phospholipids in the inner membrane of beef heart mitochondria. J Biol Chem 1979;254:5308–16.10.1016/S0021-9258(18)50596-2Search in Google Scholar

97. Comte, J, Maǐsterrena, B, Gautheron, DC. Lipid composition and protein profiles of outer and inner membranes from pig heart mitochondria. Comparison with microsomes. Biochim Biophys Acta Biomembr 1976;419:271–84. https://doi.org/10.1016/0005-2736(76)90353-9.Search in Google Scholar

98. Colbeau, A, Nachbaur, J, Vignais, PM. Enzymac characterization and lipid composition of rat liver subcellular membranes. Biochim Biophys Acta Biomembr 1971;249:462–92. https://doi.org/10.1016/0005-2736(71)90123-4.Search in Google Scholar

99. Marrink, SJ, Corradi, V, Souza, PCT, Ingólfsson, HI, Tieleman, DP, Sansom, MSP. Computational modeling of realistic cell membranes. Chem Rev 2019;119:6184–226. https://doi.org/10.1021/acs.chemrev.8b00460.Search in Google Scholar PubMed PubMed Central

100. Fleetwood, O, Kasimova, MA, Westerlund, AM, Delemotte, L. Molecular insights from conformational ensembles via machine learning. Biophys J 2020;118:765–80. https://doi.org/10.1016/j.bpj.2019.12.016.Search in Google Scholar PubMed PubMed Central

101. Invernizzi, M, Parrinello, M. Rethinking metadynamics: from bias potentials to probability distributions. J Phys Chem Lett 2020;11:2731–6. https://doi.org/10.1021/acs.jpclett.0c00497.Search in Google Scholar PubMed

102. Dalbon, P, Brandolin, G, Boulay, F, Hoppe, J, Vignais, PV. Mapping of the nucleotide-binding sites in the ADP/ATP carrier of beef heart mitochondria by photolabeling with 2-azido[α-32p]adenosine diphosphate. Biochemistry 1988;27:5141–9. https://doi.org/10.1021/bi00414a029.Search in Google Scholar PubMed

103. Crichton, PG, Lee, Y, Ruprecht, JJ, Cerson, E, Thangaratnarajah, C, King, MS, et al.. Trends in thermostability provide information on the nature of substrate, inhibitor, and lipid interactions with mitochondrial carriers. J Biol Chem 2015;290:8206–17. https://doi.org/10.1074/jbc.M114.616607.Search in Google Scholar PubMed PubMed Central

104. Giangregorio, N, Tonazzi, A, Console, L, Prejanò, M, Marino, T, Russo, N, et al.. Effect of copper on the mitochondrial carnitine/acylcarnitine carrier via interaction with Cys136 and Cys155. Possible implications in pathophysiology. Molecules 2020;25:820. https://doi.org/10.3390/molecules25040820.Search in Google Scholar PubMed PubMed Central

105. Zoonens, M, Comer, J, Masscheleyn, S, Pebay-Peyroula, E, Chipot, C, Miroux, B, et al.. Dangerous liaisons between detergents and membrane proteins. the case of mitochondrial uncoupling protein 2. J Am Chem Soc 2013;135:15174–82. https://doi.org/10.1021/ja407424v.Search in Google Scholar PubMed

106. Hoang, T, Smith, MD, Jelokhani-Niaraki, M. Toward understanding the mechanism of ion transport activity of neuronal uncoupling proteins UCP2, UCP4, and UCP5. Biochemistry 2012;51:4004–14. https://doi.org/10.1021/bi3003378.Search in Google Scholar PubMed

107. Sun, J, Aluvila, S, Kotaria, R, Mayor, JA, Walters, DE, Kaplan, RS. Mitochondrial and plasma membrane citrate transporters: discovery of selective inhibitors and application to structure/function analysis. Mol Cell Pharmacol 2010;2:101–10. https://doi.org/10.4255/mcpharmacol.10.14.Search in Google Scholar

108. Monné, M, Miniero, DV, Daddabbo, L, Robinson, AJ, Kunji, ERS, Palmieri, F. Substrate specificity of the two mitochondrial ornithine carriers can be swapped by single mutation in substrate binding site. J Biol Chem 2012;287:7925–34. https://doi.org/10.1074/jbc.M111.324855.Search in Google Scholar PubMed PubMed Central

109. Tessa, A, Fiermonte, G, Dionisi-Vici, C, Paradies, E, Baumgartner, MR, Chien, Y-H, et al.. Identification of novel mutations in the SLC25A15 gene in hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome: a clinical, molecular, and functional study. Hum Mutat 2009;30:741–8. https://doi.org/10.1002/humu.20930.Search in Google Scholar PubMed

110. Nota, B, Struys, EA, Pop, A, Jansen, EE, Fernandez Ojeda, MR, Kanhai, WA, et al.. Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria. Am J Hum Genet 2013;92:627–31. https://doi.org/10.1016/j.ajhg.2013.03.009.Search in Google Scholar PubMed PubMed Central

111. Edvardson, S, Porcelli, V, Jalas, C, Soiferman, D, Kellner, Y, Shaag, A, et al.. Agenesis of corpus callosum and optic nerve hypoplasia due to mutations in SLC25A1 encoding the mitochondrial citrate transporter. J Med Genet 2013;50:240–5. https://doi.org/10.1136/jmedgenet-2012-101485.Search in Google Scholar PubMed

112. Al‐Futaisi, A, Ahmad, F, Al‐Kasbi, G, Al‐Thihli, K, Koul, R, Al‐Maawali, A. Missense mutations in SLC25A1 are associated with congenital myasthenic syndrome type 23. Clin Genet 2020;97:666–7. https://doi.org/10.1111/cge.13678.Search in Google Scholar PubMed

113. Chaouch, A, Porcelli, V, Cox, D, Edvardson, S, Scarcia, P, De Grassi, A, et al.. Mutations in the mitochondrial citrate carrier SLC25A1 are associated with impaired neuromuscular transmission. J Neuromuscul Dis 2014;1:75–90. https://doi.org/10.3233/JND-140021.Search in Google Scholar PubMed PubMed Central

114. Balaraju, S, Töpf, A, McMacken, G, Kumar, VP, Pechmann, A, Roper, H, et al.. Congenital myasthenic syndrome with mild intellectual disability caused by a recurrent SLC25A1 variant. Eur J Hum Genet 2020;28:373–7. https://doi.org/10.1038/s41431-019-0506-2.Search in Google Scholar PubMed PubMed Central

115. Bhoj, EJ, Li, M, Ahrens-Nicklas, R, Pyle, LC, Wang, J, Zhang, VW, 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 2015;19:59–66. Springer. https://doi.org/10.1007/8904_2014_364.Search in Google Scholar PubMed PubMed Central

116. Mayr, JA, Merkel, O, Kohlwein, SD, Gebhardt, BR, Böhles, H, Fötschl, U, et al.. Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. Am J Hum Genet 2007;80:478–84. https://doi.org/10.1086/511788.Search in Google Scholar PubMed PubMed Central

117. Mayr, JA, Zimmermann, FA, Horváth, R, Schneider, HC, Schoser, B, Holinski-Feder, E, et al.. Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children. Neuromuscul Disord 2011;21:803–8. https://doi.org/10.1016/j.nmd.2011.06.005.Search in Google Scholar PubMed

118. Thompson, K, Majd, H, Dallabona, C, Reinson, K, King, MS, Alston, CL, et al.. Recurrent de novo dominant mutations in SLC25A4 cause severe early-onset mitochondrial disease and loss of mitochondrial DNA copy number. Am J Hum Genet 2016;99:860–76. https://doi.org/10.1016/j.ajhg.2016.08.014.Search in Google Scholar PubMed PubMed Central

119. Bakker, HD, Scholte, HR, Van den Bogert, C, Jeneson, JAL, Ruitenbeek, W, Wanders, RJA, et al.. Adenine nucleotide translocator deficiency in muscle: potential therapeutic value of vitamin E. J Inherit Metab Dis 1993;16:548–52. https://doi.org/10.1007/BF00711678.Search in Google Scholar PubMed

120. Bakker, HD, Scholte, HR, Van Den Bogert, C, Ruitenbeer, W, Jeneson, JAL, Wanders, RJA, et al.. Deficiency of the adenine nucleotide translocator in muscle of a patient with myopathy and lactic acidosis: a new mitochondrial defect. Pediatr Res 1993;33:412–7. https://doi.org/10.1203/00006450-199304000-00019.Search in Google Scholar PubMed

121. Echaniz-Laguna, A, Chassagne, M, Ceresuela, J, Rouvet, I, Padet, S, Acquaviva, C, et al.. Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy. J Med Genet 2012;49:146–50. https://doi.org/10.1136/jmedgenet-2011-100504.Search in Google Scholar PubMed

122. Palmieri, L, Alberio, S, Pisano, I, Lodi, T, Meznaric-Petrusa, M, Zidar, J, et al.. Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum Mol Genet 2005;14:3079–88. https://doi.org/10.1093/hmg/ddi341.Search in Google Scholar PubMed

123. Körver-Keularts, IMLW, de Visser, M, Bakker, HD, Wanders, RJA, Vansenne, F, Scholte, HR, et al.. Two novel mutations in the SLC25A4 gene in a patient with mitochondrial myopathy. JIMD Rep 2015;22:39–45. Springer. https://doi.org/10.1007/8904_2015_409.Search in Google Scholar PubMed PubMed Central

124. Kaukonen, J, Juselius, JK, Tiranti, V, Kyttala, A, Zeviani, M, Comi, GP, et al.. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 2000;289:782–5. https://doi.org/10.1126/science.289.5480.782.Search in Google Scholar PubMed

125. Napoli, L, Bordoni, A, Zeviani, M, Hadjigeorgiou, GM, Sciacco, M, Tiranti, V, et al.. A novel missense adenine nucleotide translocator-1 gene mutation in a greek adPEO family. Neurology 2001;57:2295–8. https://doi.org/10.1212/WNL.57.12.2295.Search in Google Scholar PubMed

126. Komaki, H, Fukazawa, T, Houzen, H, Yoshida, K, Nonaka, I, Goto, Y-I. A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions. Ann Neurol 2002;51:645–8. https://doi.org/10.1002/ana.10172.Search in Google Scholar PubMed

127. Punzi, G, Porcelli, V, Ruggiu, M, Hossain, MF, Menga, A, Scarcia, P, et al.. SLC25A10 biallelic mutations in intractable epileptic encephalopathy with complex I deficiency. Hum Mol Genet 2018;27:499–504. https://doi.org/10.1093/hmg/ddx419.Search in Google Scholar PubMed PubMed Central

128. Buffet, A, Morin, A, Castro-Vega, L-J, Habarou, F, Lussey-Lepoutre, C, Letouzé, E, et al.. Germline mutations in the mitochondrial 2-oxoglutarate/malate carrier SLC25A11 gene confer a predisposition to metastatic paragangliomas. Canc Res 2018;78:1914–22. https://doi.org/10.1158/0008-5472.can-17-2463.Search in Google Scholar PubMed

129. Falk, MJ, Li, D, Gai, X, McCormick, E, Place, E, Lasorsa, FM, et al.. AGC1 deficiency causes infantile epilepsy, abnormal myelination, and reduced N-acetylaspartate. JIMD Rep 2014;14:77–85. Springer. https://doi.org/10.1007/8904_2013_287.Search in Google Scholar PubMed PubMed Central

130. Wibom, R, Lasorsa, FM, Töhönen, V, Barbaro, M, Sterky, FH, Kucinski, T, et al.. AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med 2009;361:489–95. https://doi.org/10.1056/NEJMoa0900591.Search in Google Scholar PubMed

131. Kobayashi, K, Sinasac, DS, Iijima, M, Boright, AP, Begum, L, Lee, JR, et al.. The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet 1999;22:159–63. https://doi.org/10.1038/9667.Search in Google Scholar PubMed

132. Tomomasa, T, Kobayashi, K, Kaneko, H, Shimura, H, Fukusato, T, Tabata, M, et al.. Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy. J Pediatr 2001;138:741–3. https://doi.org/10.1067/mpd.2001.113361.Search in Google Scholar

133. Yasuda, T, Yamaguchi, N, Kobayashi, K, Nishi, I, Horinouchi, H, Jalil, MA, et al.. Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia. Hum Genet 2000;107:537–45. https://doi.org/10.1007/s004390000430.Search in Google Scholar

134. Fiermonte, G, Soon, D, Chaudhuri, A, Paradies, E, Lee, PJ, Krywawych, S, et al.. An adult with type 2 citrullinemia presenting in Europe. N Engl J Med 2008;358:1408–9. https://doi.org/10.1056/NEJMc0707353.Search in Google Scholar

135. Ohura, T, Kobayashi, K, Tazawa, Y, Nishi, I, Abukawa, D, Sakamoto, O, et al.. Neonatal presentation of adult-onset type II citrullinemia. Hum Genet 2001;108:87–90. https://doi.org/10.1007/s004390000448.Search in Google Scholar

136. Tamamori, A, Okano, Y, Ozaki, H, Fujimoto, A, Kajiwara, M, Fukuda, K, et al.. Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation. Eur J Pediatr 2002;161:609–13. https://doi.org/10.1007/s00431-002-1045-2.Search in Google Scholar

137. Tazawa, Y, Kobayashi, K, Ohura, T, Abukawa, D, Nishinomiya, F, Hosoda, Y, et al.. Infantile cholestatic jaundice associated with adult-onset type II citrullinemia. J Pediatr 2001;138:735–40. https://doi.org/10.1067/mpd.2001.113264.Search in Google Scholar

138. Camacho, JA, Obie, C, Biery, B, Goodman, BK, Hu, CA, Almashanu, S, et al.. Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet 1999;22:151–8. https://doi.org/10.1038/9658.Search in Google Scholar

139. Camacho, JA, Mardach, R, Rioseco-Camacho, N, Ruiz-Pesini, E, Derbeneva, O, Andrade, D, et al.. Clinical and functional characterization of a human ORNT1 mutation (T32R) in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Pediatr Res 2006;60:423–9. https://doi.org/10.1203/01.pdr.0000238301.25938.f5.Search in Google Scholar

140. Miyamoto, T, Kanazawa, N, Kato, S, Kawakami, M, Inoue, Y, Kuhara, T, et al.. Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X. J Hum Genet 2001;46:260–2. https://doi.org/10.1007/s100380170075.Search in Google Scholar

141. Nakajima, M, Ishii, S, Mito, T, Takeshita, K, Takashima, S, Takakura, H, et al.. Clinical, biochemical and ultrastructural study on the pathogenesis of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. Brain Dev 1988;10:181–5. https://doi.org/10.1016/S0387-7604(88)80025-1.Search in Google Scholar

142. Salvi, S, Santorelli, FM, Bertini, E, Boldrini, R, Meli, C, Donati, A, et al.. Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. Neurology 2001;57:911–4. https://doi.org/10.1212/WNL.57.5.911.Search in Google Scholar PubMed

143. Rosenberg, MJ, Agarwala, R, Bouffard, G, Davis, J, Fiermonte, G, Hilliard, MS, et al.. Mutant deoxynucleotide carrier is associated with congenital microcephaly. Nat Genet 2002;32:175–9. https://doi.org/10.1038/ng948.Search in Google Scholar PubMed

144. Spiegel, R, Shaag, A, Edvardson, S, Mandel, H, Stepensky, P, Shalev, SA, et al.. SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis. Ann Neurol 2009;66:419–24. https://doi.org/10.1002/ana.21752.Search in Google Scholar PubMed

145. Huizing, M, Wendel, U, Ruitenbeek, W, Iacobazzi, V, Ijlst, L, Veenhuizen, P, et al.. Carnitine-acylcarnitine carrier deficiency: identification of the molecular defect in a patient. J Inherit Metab Dis 1998;21:262–7. https://doi.org/10.1023/A:1005324323401.10.1023/A:1005324323401Search in Google Scholar

146. Huizing, M, Iacobazzi, V, Ijlst, L, Savelkoul, P, Ruitenbeek, W, Van Den Heuvel, L, et al.. Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am J Hum Genet 1997;61:1239–45. https://doi.org/10.1086/301628.Search in Google Scholar PubMed PubMed Central

147. Costa, C, Costa, JM, Nuoffer, JM, Slama, A, Boutron, A, Saudubray, JM, et al.. Identification of the molecular defect in a severe case of carnitine-acylcarnitine carrier deficiency. J Inherit Metab Dis 1999;22:267–70. https://doi.org/10.1023/A:1005590223680.10.1023/A:1005590223680Search in Google Scholar

148. Ogawa, A, Yamamoto, S, Kanazawa, M, Takayanagi, M, Hasegawa, S, Kohno, Y. Identification of two novel mutations of the carnitine/acylcarnitine translocase (CACT) gene in a patient with CACT deficiency. J Hum Genet 2000;45:52–5. https://doi.org/10.1007/s100380050010.Search in Google Scholar PubMed

149. Stanley, CA, Hale, DE, Berry, GT, Deleeuw, S, Boxer, J, Bonnefont, J-P. A deficiency of carnitine–acylcarnitine translocase in the inner mitochondrial membrane. N Engl J Med 1992;327:19–23. https://doi.org/10.1056/NEJM199207023270104.Search in Google Scholar PubMed

150. Fukushima, T, Kaneoka, H, Yasuno, T, Sasaguri, Y, Tokuyasu, T, Tokoro, K, et al.. Three novel mutations in the carnitine-acylcarnitine translocase (CACT) gene in patients with CACT deficiency and in healthy individuals. J Hum Genet 2013;58:788–93. https://doi.org/10.1038/jhg.2013.103.Search in Google Scholar PubMed

151. Al Aqeel, AI, Rashid, MS, Pn Ruiter, J, Ijlst, L, Ja Wanders, R. A novel molecular defect of the carnitine acylcarnitine translocase gene in a Saudi patient. Clin Genet 2003;64:163–5. https://doi.org/10.1034/j.1399-0004.2003.00117.x.Search in Google Scholar PubMed

152. Iacobazzi, V, Pasquali, M, Singh, R, Matern, D, Rinaldo, P, di San Filippo, CA, et al.. Response to therapy in carnitine/acylcarnitine translocase (CACT) deficiency due to a novel missense mutation. Am J Med Genet 2004;126A:150–5. https://doi.org/10.1002/ajmg.a.20573.Search in Google Scholar

153. Boczonadi, V, King, MS, Smith, AC, Olahova, M, Bansagi, B, Roos, A, et al.. Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease. Genet Med 2018;20:1224–35. https://doi.org/10.1038/gim.2017.251.Search in Google Scholar

154. Molinari, F, Kaminska, A, Fiermonte, G, Boddaert, N, Raas-Rothschild, A, Plouin, P, et al.. Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts. Clin Genet 2009;76:188–94. https://doi.org/10.1111/j.1399-0004.2009.01236.x.Search in Google Scholar

155. Molinari, F, Raas-Rothschild, A, Rio, M, Fiermonte, G, Encha-Razavi, F, Palmieri, L, et al.. Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy. Am J Hum Genet 2005;76:334–9. https://doi.org/10.1086/427564.Search in Google Scholar

156. Poduri, A, Heinzen, EL, Chitsazzadeh, V, Lasorsa, FM, Elhosary, PC, LaCoursiere, CM, et al.. SLC25A22 is a novel gene for migrating partial seizures in infancy. Ann Neurol 2013;74:873–82. https://doi.org/10.1002/ana.23998.Search in Google Scholar

157. Adolphs, N, Klein, M, Haberl, EJ, Graul-Neumann, L, Menneking, H, Hoffmeister, B. Necrotizing soft tissue infection of the scalp after fronto-facial advancement by internal distraction in a 7-year old girl with Gorlin–Chaudhry–Moss syndrome – a case report. J Cranio-Maxillofacial Surg 2011;39:554–61. https://doi.org/10.1016/j.jcms.2010.11.016.Search in Google Scholar

158. Ehmke, N, Graul-Neumann, L, Smorag, L, Koenig, R, Segebrecht, L, Magoulas, P, et al.. De novo mutations in SLC25A24 cause a craniosynostosis syndrome with hypertrichosis, progeroid appearance, and mitochondrial dysfunction. Am J Hum Genet 2017;101:833–43. https://doi.org/10.1016/j.ajhg.2017.09.016.Search in Google Scholar

159. Faivre, L, Van Kien, PK, Madinier-Chappat, N, Nivelon-Chevallier, A, Beer, F, LeMerrer, M. Can Hutchinson-Gilford progeria syndrome be a neonatal condition? Am J Med Genet 1999;87:450–2. https://doi.org/10.1002/(SICI)1096-8628(19991222)87:5<450::AID-AJMG16>3.0.CO;2-T.10.1002/(SICI)1096-8628(19991222)87:5<450::AID-AJMG16>3.0.CO;2-TSearch in Google Scholar

160. Castori, M, Silvestri, E, Pedace, L, Marseglia, G, Tempera, A, Antigoni, I, et al.. Fontaine–Farriaux syndrome: a recognizable craniosynostosis syndrome with nail, skeletal, abdominal, and central nervous system anomalies. Am J Med Genet Part A 2009;149A:2193–9. https://doi.org/10.1002/ajmg.a.32763.Search in Google Scholar

161. Writzl, K, Maver, A, Kovačič, L, Martinez-Valero, P, Contreras, L, Satrustegui, J, et al.. De novo mutations in SLC25A24 cause a disorder characterized by early aging, bone dysplasia, characteristic face, and early demise. Am J Hum Genet 2017;101:844–55. https://doi.org/10.1016/j.ajhg.2017.09.017.Search in Google Scholar

162. Rodríguez, JI, Pérez-Alonso, P, Funes, R, Pérez-Rodríguez, J. Lethal neonatal Hutchinson-Gilford progeria syndrome. Am J Med Genet 1999;82:242–8. https://doi.org/10.1002/(SICI)1096-8628(19990129)82:3<242::AID-AJMG9>3.0.CO;2-E.10.1002/(SICI)1096-8628(19990129)82:3<242::AID-AJMG9>3.0.CO;2-ESearch in Google Scholar

163. Kishita, Y, Pajak, A, Bolar, NA, Marobbio, CMT, Maffezzini, C, Miniero, DV, et al.. Intra-mitochondrial methylation deficiency due to mutations in SLC25A26. Am J Hum Genet 2015;97:761–8. https://doi.org/10.1016/j.ajhg.2015.09.013.Search in Google Scholar

164. Schiff, M, Veauville-Merllié, A, Su, CH, Tzagoloff, A, Rak, M, Ogier de Baulny, H, et al.. SLC25A32 mutations and riboflavin-responsive exercise intolerance. N Engl J Med 2016;374:795–7. https://doi.org/10.1056/nejmc1513610.Search in Google Scholar

165. Guernsey, DL, Jiang, H, Campagna, DR, Evans, SC, Ferguson, M, Kellogg, MD, et al.. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Nat Genet 2009;41:651–3. https://doi.org/10.1038/ng.359.Search in Google Scholar

166. Almannai, M, Alasmari, A, Alqasmi, A, Faqeih, E, Al Mutairi, F, Alotaibi, M, et al.. Expanding the phenotype of SLC25A42-associated mitochondrial encephalomyopathy. Clin Genet 2018;93:1097–102. https://doi.org/10.1111/cge.13210.Search in Google Scholar

167. Iuso, A, Alhaddad, B, Weigel, C, Kotzaeridou, U, Mastantuono, E, Schwarzmayr, T, et al.. A homozygous splice site mutation in SLC25A42, encoding the mitochondrial transporter of coenzyme a, causes metabolic crises and epileptic encephalopathy. JIMD Rep 2019;44:1–7. Springer. https://doi.org/10.1007/8904_2018_115.Search in Google Scholar

168. Shamseldin, HE, Smith, LL, Kentab, A, Alkhalidi, H, Summers, B, Alsedairy, H, et al.. Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans. Hum Genet 2016;135:21–30. https://doi.org/10.1007/s00439-015-1608-8.Search in Google Scholar

169. Abrams, AJ, Hufnagel, RB, Rebelo, A, Zanna, C, Patel, N, Gonzalez, MA, et al.. Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Nat Genet 2015;47:926–32. https://doi.org/10.1038/ng.3354.Search in Google Scholar

170. Wan, J, Steffen, J, Yourshaw, M, Mamsa, H, Andersen, E, Rudnik-Schöneborn, S, et al.. Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia. Brain 2016;139:2877–90. https://doi.org/10.1093/brain/aww212.Search in Google Scholar

171. Charlesworth, G, Balint, B, Mencacci, NE, Carr, L, Wood, NW, Bhatia, KP. SLC25A46 mutations underlie progressive myoclonic ataxia with optic atrophy and neuropathy. Mov Disord 2016;31:1249–51. https://doi.org/10.1002/mds.26716.Search in Google Scholar

172. Janer, A, Prudent, J, Paupe, V, Fahiminiya, S, Majewski, J, Sgarioto, N, et al.. SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. EMBO Mol Med 2016;8:1019–38. https://doi.org/10.15252/emmm.201506159.Search in Google Scholar

173. Esterbauer, H, Schneitler, C, Oberkofler, H, Ebenbichler, C, Paulweber, B, Sandhofer, F, et al.. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet 2001;28:178–83. https://doi.org/10.1038/88911.Search in Google Scholar

174. Bulotta, A, Ludovico, O, Coco, A, Di Paola, R, Quattrone, A, Carella, M, et al.. The common −866G/A polymorphism in the promoter region of the UCP-2 gene is associated with reduced risk of type 2 diabetes in Caucasians from Italy. J Clin Endocrinol Metab 2005;90:1176–80. https://doi.org/10.1210/jc.2004-1072.Search in Google Scholar

175. Argyropoulos, G, Brown, AM, Willi, SM, Zhu, J, He, Y, Reitman, M, et al.. Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. J Clin Invest 1998;102:1345–51. https://doi.org/10.1172/JCI4115.Search in Google Scholar

176. Brown, AM, Willi, SM, Argyropoulos, G, Garvey, WT. A novel missense mutation, R70W, in the human uncoupling protein 3 gene in a family with type 2 diabetes. Hum Mutat 1999;13:506. https://doi.org/10.1002/(SICI)1098-1004(1999)13:6<506::AID-HUMU19>3.0.CO;2-P.10.1002/(SICI)1098-1004(1999)13:6<506::AID-HUMU19>3.0.CO;2-PSearch in Google Scholar

177. Pettersen, EF, Goddard, TD, Huang, CC, Couch, GS, Greenblatt, DM, Meng, EC, et al.. UCSF Chimera – a visualization system for exploratory research and analysis. J Comput Chem 2004;25:1605–12. https://doi.org/10.1002/jcc.20084.Search in Google Scholar