1932

Abstract

Members of the mitochondrial carrier family [solute carrier family 25 (SLC25)] transport nucleotides, amino acids, carboxylic acids, fatty acids, inorganic ions, and vitamins across the mitochondrial inner membrane. They are important for many cellular processes, such as oxidative phosphorylation of lipids and sugars, amino acid metabolism, macromolecular synthesis, ion homeostasis, cellular regulation, and differentiation. Here, we describe the functional elements of the transport mechanism of mitochondrial carriers, consisting of one central substrate-binding site and two gates with salt-bridge networks on either side of the carrier. Binding of the substrate during import causes three gate elements to rotate inward, forming the cytoplasmic network and closing access to the substrate-binding site from the intermembrane space. Simultaneously, three core elements rock outward, disrupting the matrix network and opening the substrate-binding site to the matrix side of the membrane. During export, substrate binding triggers conformational changes involving the same elements but operating in reverse.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-072820-020508
2021-06-20
2024-10-14
Loading full text...

Full text loading...

/deliver/fulltext/biochem/90/1/annurev-biochem-072820-020508.html?itemId=/content/journals/10.1146/annurev-biochem-072820-020508&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Mitchell P. 1961. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–48
    [Google Scholar]
  2. 2. 
    Mitchell P. 2011. 1966. Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biochim. Biophys. Acta Bioenerg. 1807:1507–38Reprint of Peter Mitchell's classic review on the chemiosmotic theory—the foundation of modern bioenergetics.
    [Google Scholar]
  3. 3. 
    Chappell JB. 1968. Systems used for the transport of substrates into mitochondria. Br. Med. Bull. 24:150–57Review of the early discoveries of mitochondrial carriers and their links to metabolism.
    [Google Scholar]
  4. 4. 
    Bruni A, Luciani S. 1962. Effects of atractyloside and oligomycin on magnesium-stimulated adenosine triphosphatase and on adenosine triphosphate-induced contraction of swollen mitochondria. Nature 196:578–80
    [Google Scholar]
  5. 5. 
    Vignais PV, Vignais PM, Stanislas E. 1962. Action of potassium atractylate on oxidative phosphorylation in mitochondria and in submitochondrial particles. Biochim. Biophys. Acta 60:284–300
    [Google Scholar]
  6. 6. 
    Bruni A, Contessa AR, Luciani S. 1962. Atractyloside as inhibitor of energy-transfer reactions in liver mitochondria. Biochim. Biophys. Acta 60:301–16
    [Google Scholar]
  7. 7. 
    Kemp A Jr., Slater EC. 1964. The site of action of atractyloside. Biochim. Biophys. Acta Specialized Sect. Enzymol. Subj. 92:178–80
    [Google Scholar]
  8. 8. 
    Chappell JB, Crofts AR. 1965. The effect of atractylate and oligomycin on the behaviour of mitochondria towards adenine nucleotides. Biochem. J. 95:707–16
    [Google Scholar]
  9. 9. 
    Pfaff E, Klingenberg M, Heldt HW. 1965. Unspecific permeation and specific exchange of adenine nucleotides in liver mitochondria. Biochim. Biophys. Acta Gen. Subj. 104:312–15
    [Google Scholar]
  10. 10. 
    Heldt HW, Jacobs H, Klingenberg M. 1965. Endogenous ADP of mitochondria, an early phosphate acceptor of oxidative phosphorylation as disclosed by kinetic studies with C14 labelled ADP and ATP and with atractyloside. Biochem. Biophys. Res. Commun. 18:174–79
    [Google Scholar]
  11. 11. 
    Duee ED, Vignais PV. 1965. Exchange between extra- and intramitochondrial adenine nucleotides. Biochim. Biophys. Acta Gen. Subj. 107:184–88
    [Google Scholar]
  12. 12. 
    Winkler HH, Bygrave FL, Lehninger AL. 1968. Characterization of the atractyloside-sensitive adenine nucleotide transport system in rat liver mitochondria. J. Biol. Chem. 243:20–28
    [Google Scholar]
  13. 13. 
    Henderson PJ, Lardy HA. 1970. Bongkrekic acid. An inhibitor of the adenine nucleotide translocase of mitochondria. J. Biol. Chem. 245:1319–26
    [Google Scholar]
  14. 14. 
    Lauquin GJ, Duplaa AM, Klein G, Rousseau A, Vignais PV. 1976. Isobongkrekic acid, a new inhibitor of mitochondrial ADP–ATP transport: radioactive labeling and chemical and biological properties. Biochemistry 15:2323–27
    [Google Scholar]
  15. 15. 
    Luciani S, Martini N, Santi R. 1971. Effects of carboxyatractyloside a structural analogue of atractyloside on mitochondrial oxidative phosphorylation. Life Sci. II 10:961–68
    [Google Scholar]
  16. 16. 
    Vignais PV, Vignais PM, Defaye G. 1971. Gummiferin, an inhibitor of the adenine-nucleotide translocation. Study of its binding properties to mitochondria. FEBS Lett 17:281–88
    [Google Scholar]
  17. 17. 
    Erdelt H, Weidemann MJ, Buchholz M, Klingenberg M. 1972. Some principle effects of bongkrekic acid on the binding of adenine nucleotides to mitochondrial membranes. Eur. J. Biochem. 30:107–22
    [Google Scholar]
  18. 18. 
    Klingenberg M, Buchholz M. 1973. On the mechanism of bongkrekate effect on the mitochondrial adenine-nucleotide carrier as studied through the binding of ADP. Eur. J. Biochem. 38:346–58
    [Google Scholar]
  19. 19. 
    Mitchell P. 1957. A general theory of membrane transport from studies of bacteria. Nature 180:134–36
    [Google Scholar]
  20. 20. 
    Jardetzky O. 1966. Simple allosteric model for membrane pumps. Nature 211:969–70
    [Google Scholar]
  21. 21. 
    Klingenberg M. 2008. The ADP and ATP transport in mitochondria and its carrier. Biochim. Biophys. Acta Biomembr. 1778:1978–2021Review of the discovery of the fundamental transport properties of the mitochondrial ADP/ATP carrier.
    [Google Scholar]
  22. 22. 
    Papa S, Paradies G. 1974. On the mechanism of translocation of pyruvate and other monocarboxylic acids in rat-liver mitochondria. Eur. J. Biochem. 49:265–74
    [Google Scholar]
  23. 23. 
    Pande SV. 1975. A mitochondrial carnitine acylcarnitine translocase system. PNAS 72:883–87
    [Google Scholar]
  24. 24. 
    Gamble JG, Lehninger AL. 1973. Transport of ornithine and citrulline across the mitochondrial membrane. J. Biol. Chem. 248:610–18
    [Google Scholar]
  25. 25. 
    Nicholls DG. 1976. Hamster brown-adipose-tissue mitochondria. Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site.. Eur. J. Biochem. 62:223–28
    [Google Scholar]
  26. 26. 
    Riccio P, Aquila H, Klingenberg M. 1975. Solubilization of the carboxy-atractylate binding protein from mitochondria. FEBS Lett 56:129–32
    [Google Scholar]
  27. 27. 
    Riccio P, Aquila H, Klingenberg M. 1975. Purification of the carboxy-atractylate binding protein from mitochondria. FEBS Lett 56:133–38
    [Google Scholar]
  28. 28. 
    Aquila H, Misra D, Eulitz M, Klingenberg M. 1982. Complete amino acid sequence of the ADP/ATP carrier from beef heart mitochondria. Hoppe Seylers Z Physiol. Chem. 363:345–49
    [Google Scholar]
  29. 29. 
    Saraste M, Walker JE. 1982. Internal sequence repeats and the path of polypeptide in mitochondrial ADP/ATP translocase. FEBS Lett 144:250–54
    [Google Scholar]
  30. 30. 
    Aquila H, Link TA, Klingenberg M. 1985. The uncoupling protein from brown fat mitochondria is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane. EMBO J 4:2369–76
    [Google Scholar]
  31. 31. 
    Runswick MJ, Walker JE, Bisaccia F, Iacobazzi V, Palmieri F. 1990. Sequence of the bovine 2-oxoglutarate/malate carrier protein: structural relationship to other mitochondrial transport proteins. Biochemistry 29:11033–40
    [Google Scholar]
  32. 32. 
    Runswick MJ, Powell SJ, Nyren P, Walker JE. 1987. Sequence of the bovine mitochondrial phosphate carrier protein: structural relationship to ADP/ATP translocase and the brown fat mitochondria uncoupling protein. EMBO J 6:1367–73
    [Google Scholar]
  33. 33. 
    Walker JE. 1992. The mitochondrial transporter family. Curr. Opin. Struct. Biol. 2:519–26
    [Google Scholar]
  34. 34. 
    Kunji ERS, Harding M. 2003. Projection structure of the atractyloside-inhibited mitochondrial ADP/ATP carrier of Saccharomyces cerevisiae. J. Biol. Chem. 278:36985–88
    [Google Scholar]
  35. 35. 
    Palmieri F, Scarcia P, Monne M. 2020. Diseases caused by mutations in mitochondrial carrier genes SLC25: a review. Biomolecules 10:655Review of the role of mitochondrial carriers in cellular metabolism and human diseases.
    [Google Scholar]
  36. 36. 
    Palmieri L, Lasorsa FM, Vozza A, Agrimi G, Fiermonte G et al. 2000. Identification and functions of new transporters in yeast mitochondria. Biochim. Biophys. Acta Bioenerg. 1459:363–69
    [Google Scholar]
  37. 37. 
    Palmieri F. 2014. Mitochondrial transporters of the SLC25 family and associated diseases: a review. J. Inherit. Metab. Dis. 37:565–75
    [Google Scholar]
  38. 38. 
    Kunji ERS, King MS, Ruprecht JJ, Thangaratnarajah C. 2020. The SLC25 carrier family: important transport proteins in mitochondrial physiology and pathology. Physiology 35:302–27Review of the effect of pathogenic mutations on the transport cycle of mitochondrial carriers associated with human diseases.
    [Google Scholar]
  39. 39. 
    Hediger MA, Clemencon B, Burrier RE, Bruford EA. 2013. The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol. Aspects Med. 34:95–107
    [Google Scholar]
  40. 40. 
    Herzig S, Raemy E, Montessuit S, Veuthey JL, Zamboni N et al. 2012. Identification and functional expression of the mitochondrial pyruvate carrier. Science 337:93–96
    [Google Scholar]
  41. 41. 
    Bricker DK, Taylor EB, Schell JC, Orsak T, Boutron A et al. 2012. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science 337:96–100
    [Google Scholar]
  42. 42. 
    Tavoulari S, Thangaratnarajah C, Mavridou V, Harbour ME, Martinou JC, Kunji ERS. 2019. The yeast mitochondrial pyruvate carrier is a hetero-dimer in its functional state. EMBO J 38:e100785
    [Google Scholar]
  43. 43. 
    Nury H, Dahout-Gonzalez C, Trezeguet V, Lauquin G, Brandolin G, Pebay-Peyroula E. 2005. Structural basis for lipid-mediated interactions between mitochondrial ADP/ATP carrier monomers. FEBS Lett 579:6031–36
    [Google Scholar]
  44. 44. 
    Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trezeguet V, Lauquin GJ, Brandolin G. 2003. Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 426:39–44First structure of the carboxyatractyloside-inhibited cytoplasmic state of the ADP/ATP carrier, defining the topology and matrix salt-bridge network.
    [Google Scholar]
  45. 45. 
    Ruprecht JJ, Hellawell AM, Harding M, Crichton PG, McCoy AJ, Kunji ERS 2014. Structures of yeast mitochondrial ADP/ATP carriers support a domain-based alternating-access transport mechanism. PNAS 111:E426–34Structures of the yeast ADP/ATP carriers, defining the glutamine braces, cytoplasmic salt-bridge network, and domain-based mechanism.
    [Google Scholar]
  46. 46. 
    Crichton PG, Lee Y, Ruprecht JJ, Cerson E, Thangaratnarajah C et al. 2015. Trends in thermostability provide information on the nature of substrate, inhibitor, and lipid interactions with mitochondrial carriers. J. Biol. Chem. 290:8206–17
    [Google Scholar]
  47. 47. 
    Ruprecht JJ, King MS, Zogg T, Aleksandrova AA, Pardon E et al. 2019. The molecular mechanism of transport by the mitochondrial ADP/ATP carrier. Cell 176:435–47.e15First structure of the bongkrekic acid–inhibited matrix state of the ADP/ATP carrier, defining the tyrosine braces, and core and gate elements.
    [Google Scholar]
  48. 48. 
    Uchanski T, Pardon E, Steyaert J. 2020. Nanobodies to study protein conformational states. Curr. Opin. Struct. Biol. 60:117–23
    [Google Scholar]
  49. 49. 
    Kunji ERS, Robinson AJ. 2006. The conserved substrate binding site of mitochondrial carriers. Biochim. Biophys. Acta Bioenerg. 1757:1237–48
    [Google Scholar]
  50. 50. 
    Robinson AJ, Kunji ERS 2006. Mitochondrial carriers in the cytoplasmic state have a common substrate binding site. PNAS 103:2617–22First description of the contact points and residues of the substrate-binding site of mitochondrial carriers, highlighting charge neutralization as a principle.
    [Google Scholar]
  51. 51. 
    Robinson AJ, Overy C, Kunji ERS 2008. The mechanism of transport by mitochondrial carriers based on analysis of symmetry. PNAS 105:17766–71Analyzes sequence symmetry and first describes the cytoplasmic salt-bridge network, substrate-binding site, and other key residues in the mechanism.
    [Google Scholar]
  52. 52. 
    Dehez F, Pebay-Peyroula E, Chipot C. 2008. Binding of ADP in the mitochondrial ADP/ATP carrier is driven by an electrostatic funnel. J. Am. Chem. Soc. 130:12725–33
    [Google Scholar]
  53. 53. 
    Wang Y, Tajkhorshid E 2008. Electrostatic funneling of substrate in mitochondrial inner membrane carriers. PNAS 105:9598–603
    [Google Scholar]
  54. 54. 
    Mifsud J, Ravaud S, Krammer EM, Chipot C, Kunji ERS et al. 2013. The substrate specificity of the human ADP/ATP carrier AAC1. Mol. Membr. Biol. 30:160–68
    [Google Scholar]
  55. 55. 
    Kunji ERS, Aleksandrova A, King MS, Majd H, Ashton VL et al. 2016. The transport mechanism of the mitochondrial ADP/ATP carrier. Biochim. Biophys. Acta Mol. Cell Res. 1863:2379–93
    [Google Scholar]
  56. 56. 
    Dalbon P, Brandolin G, Boulay F, Hoppe J, Vignais PV. 1988. 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 27:5141–49
    [Google Scholar]
  57. 57. 
    Nelson DR, Felix CM, Swanson JM. 1998. Highly conserved charge-pair networks in the mitochondrial carrier family. J. Mol. Biol. 277:285–308
    [Google Scholar]
  58. 58. 
    King MS, Kerr M, Crichton PG, Springett R, Kunji ERS. 2016. Formation of a cytoplasmic salt bridge network in the matrix state is a fundamental step in the transport mechanism of the mitochondrial ADP/ATP carrier. Biochim. Biophys. Acta Bioenerg. 1857:14–22
    [Google Scholar]
  59. 59. 
    Springett R, King MS, Crichton PG, Kunji ERS. 2017. Modelling the free energy profile of the mitochondrial ADP/ATP carrier. Biochim. Biophys. Acta Bioenerg. 1858:906–14
    [Google Scholar]
  60. 60. 
    Cappello AR, Curcio R, Valeria Miniero D, Stipani I, Robinson AJ et al. 2006. Functional and structural role of amino acid residues in the even-numbered transmembrane α-helices of the bovine mitochondrial oxoglutarate carrier. J. Mol. Biol. 363:51–62
    [Google Scholar]
  61. 61. 
    Cappello AR, Miniero DV, Curcio R, Ludovico A, Daddabbo L et al. 2007. Functional and structural role of amino acid residues in the odd-numbered transmembrane α-helices of the bovine mitochondrial oxoglutarate carrier. J. Mol. Biol. 369:400–12
    [Google Scholar]
  62. 62. 
    Thangaratnarajah C, Ruprecht JJ, Kunji ERS. 2014. Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. Nat. Commun. 5:5491
    [Google Scholar]
  63. 63. 
    Gifford JL, Walsh MP, Vogel HJ. 2007. Structures and metal-ion-binding properties of the Ca2+-binding helix-loop-helix EF-hand motifs. Biochem. J. 405:199–221
    [Google Scholar]
  64. 64. 
    Kunji ERS, Crichton PG. 2010. Mitochondrial carriers function as monomers. Biochim. Biophys. Acta Bioenerg. 1797:817–31
    [Google Scholar]
  65. 65. 
    Kunji ERS, Ruprecht J. 2020. The mitochondrial ADP/ATP carrier exists and functions as a monomer. Biochem. Soc. Trans. 48:1419–32
    [Google Scholar]
  66. 66. 
    Yang Q, Bruschweiler S, Chou JJ. 2014. A self-sequestered calmodulin-like Ca2+ sensor of mitochondrial SCaMC carrier and its implication to Ca2+-dependent ATP-Mg/Pi transport. Structure 22:209–17
    [Google Scholar]
  67. 67. 
    Harborne SP, Ruprecht JJ, Kunji ERS. 2015. Calcium-induced conformational changes in the regulatory domain of the human mitochondrial ATP-Mg/Pi carrier. Biochim. Biophys. Acta Bioenerg. 1847:1245–53
    [Google Scholar]
  68. 68. 
    Harborne SP, King MS, Crichton PG, Kunji ERS. 2017. Calcium regulation of the human mitochondrial ATP-Mg/Pi carrier SLC25A24 uses a locking pin mechanism. Sci. Rep. 7:45383
    [Google Scholar]
  69. 69. 
    Harborne SPD, Kunji ERS. 2018. Calcium-regulated mitochondrial ATP-Mg/Pi carriers evolved from a fusion of an EF-hand regulatory domain with a mitochondrial ADP/ATP carrier-like domain. IUBMB Life 70:1222–32
    [Google Scholar]
  70. 70. 
    Ruprecht JJ, Kunji ERS. 2019. Structural changes in the transport cycle of the mitochondrial ADP/ATP carrier. Curr. Opin. Struct. Biol. 57:135–44
    [Google Scholar]
  71. 71. 
    Klingenberg M. 2005. Ligand-protein interaction in biomembrane carriers. The induced transition fit of transport catalysis. Biochemistry 44:8563–70
    [Google Scholar]
  72. 72. 
    Beyer K, Klingenberg M. 1985. ADP/ATP carrier protein from beef heart mitochondria has high amounts of tightly bound cardiolipin, as revealed by 31P nuclear magnetic resonance. Biochemistry 24:3821–26
    [Google Scholar]
  73. 73. 
    Lee Y, Willers C, Kunji ERS, Crichton PG 2015. Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin. PNAS 112:6973–78
    [Google Scholar]
  74. 74. 
    Duncan AL, Ruprecht JJ, Kunji ERS, Robinson AJ. 2018. Cardiolipin dynamics and binding to conserved residues in the mitochondrial ADP/ATP carrier. Biochim. Biophys. Acta Biomembr. 1860:1035–45
    [Google Scholar]
  75. 75. 
    Dehez F, Schanda P, King MS, Kunji ERS, Chipot C. 2017. Mitochondrial ADP/ATP carrier in dodecylphosphocholine binds cardiolipins with non-native affinity. Biophys. J. 113:2311–15
    [Google Scholar]
  76. 76. 
    Brandolin G, Doussiere J, Gulik A, Gulik-Krzywicki T, Lauquin GJ, Vignais PV. 1980. Kinetic, binding and ultrastructural properties of the beef heart adenine nucleotide carrier protein after incorporation into phospholipid vesicles. Biochim. Biophys. Acta Bioenerg. 592:592–614
    [Google Scholar]
  77. 77. 
    Krämer R, Klingenberg M. 1980. Enhancement of reconstituted ADP,ATP exchange activity by phosphatidylethanolamine and by anionic phospholipids. FEBS Lett 119:257–60
    [Google Scholar]
  78. 78. 
    Jiang F, Rizavi HS, Greenberg ML. 1997. Cardiolipin is not essential for the growth of Saccharomyces cerevisiae on fermentable or non-fermentable carbon sources. Mol. Microbiol. 26:481–91
    [Google Scholar]
  79. 79. 
    Jiang F, Ryan MT, Schlame M, Zhao M, Gu Z et al. 2000. Absence of cardiolipin in the crd1 null mutant results in decreased mitochondrial membrane potential and reduced mitochondrial function. J. Biol. Chem. 275:22387–94
    [Google Scholar]
  80. 80. 
    Bamber L, Harding M, Butler PJG, Kunji ERS 2006. Yeast mitochondrial ADP/ATP carriers are monomeric in detergents. PNAS 103:16224–29
    [Google Scholar]
  81. 81. 
    Bamber L, Harding M, Monné M, Slotboom DJ, Kunji ERS 2007. The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes. PNAS 104:10830–34
    [Google Scholar]
  82. 82. 
    Bamber L, Slotboom DJ, Kunji ERS. 2007. Yeast mitochondrial ADP/ATP carriers are monomeric in detergents as demonstrated by differential affinity purification. J. Mol. Biol. 371:388–95
    [Google Scholar]
  83. 83. 
    Lee Y, Willers C, Kunji ERS, Crichton PG 2015. Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin. PNAS 112:6973–78
    [Google Scholar]
  84. 84. 
    Kunji ERS, Harding M, Butler PJG, Akamine P. 2008. Determination of the molecular mass and dimensions of membrane proteins by size exclusion chromatography. Methods 46:62–72
    [Google Scholar]
  85. 85. 
    Miniero DV, Cappello AR, Curcio R, Ludovico A, Daddabbo L et al. 2011. Functional and structural role of amino acid residues in the matrix α-helices, termini and cytosolic loops of the bovine mitochondrial oxoglutarate carrier. Biochim. Biophys. Acta Bioenerg. 1807:302–10
    [Google Scholar]
  86. 86. 
    Krämer R, Palmieri F 1992. Metabolite carriers in mitochondria. Molecular Mechanism in Bioenergetics L Ernster 359–84 Amsterdam: Elsevier Sci.
    [Google Scholar]
  87. 87. 
    Kunji ERS, Robinson AJ. 2010. Coupling of proton and substrate translocation in the transport cycle of mitochondrial carriers. Curr. Opin. Struct. Biol. 20:440–47
    [Google Scholar]
  88. 88. 
    Ruprecht JJ, Kunji ERS. 2020. The SLC25 mitochondrial carrier family: structure and mechanism. Trends Biochem. Sci. 45:244–58
    [Google Scholar]
  89. 89. 
    Klingenberg M. 1980. The ADP-ATP translocation in mitochondria, a membrane potential controlled transport. J. Membr. Biol. 56:97–105
    [Google Scholar]
  90. 90. 
    Gropp T, Brustovetsky N, Klingenberg M, Muller V, Fendler K, Bamberg E. 1999. Kinetics of electrogenic transport by the ADP/ATP carrier. Biophys. J. 77:714–26
    [Google Scholar]
  91. 91. 
    Majd H, King MS, Palmer SM, Smith AC, Elbourne LD et al. 2018. Screening of candidate substrates and coupling ions of transporters by thermostability shift assays. eLife 7:e38821
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-072820-020508
Loading
/content/journals/10.1146/annurev-biochem-072820-020508
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error