Journal of Bioenergetics and Biomembranes

, Volume 30, Issue 3, pp 277–284

Human Mitochondrial Transmembrane Metabolite Carriers: Tissue Distribution and Its Implication for Mitochondrial Disorders

  • Marjan Huizing
  • Wim Ruitenbeek
  • Lambert P. van den Heuvel
  • Vincenza Dolce
  • Vito Iacobazzi
  • Jan A. M. Smeitink
  • Ferdinando Palmieri
  • J. M. Frans Trijbels


Mitochondrial transmembrane carrier deficiencies are a recently discovered group of disorders, belonging to the so-called mitochondriocytopathies. We examined the human tissue distribution of carriers which are involved in the process of oxidative phosphorylation (adenine nucleotide translocator, phosphate carrier, and voltage-dependent anion channel) and some mitochondrial substrate carriers (2-oxoglutarate carrier, carnitine-acylcarnitine carrier, and citrate carrier). The tissue distribution on mRNA level of mitochondrial transport proteins appears to be roughly in correlation with the dependence of these tissues on mitochondrial energy production capacity. In general the main mRNA expression of carriers involved in mitochondrial energy metabolism occurs in skeletal muscle and heart. Expression in liver and pancreas differs between carriers. Expression in brain, placenta, lung, and kidney is lower than in the other tissues. Western and Northern blotting experiments show a comparable HVDAC1 protein and mRNA distribution for the tested tissues. Patient's studies showed that cultured skin fibroblasts may not be a reliable alternative for skeletal muscle in screening for human mitochondrial carrier defects.

Mitochondrial transmembrane carrier tissue distribution mitochondriopathy adenine nucleotide translocator phosphate carrier voltage-dependent anion channel citrate carrier oxoglutarate carrier carnitine-acylcarnitine carrier 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Babel, D., Walter, G., Götz, H., Thinnes, F. P., Jürgens, L., Köning, U., and Hilschmann, N. (1991). Biol. Chem. Hoppe Seyler 372, 1027-1034.PubMedGoogle Scholar
  2. Bakker, H. D., Scholte, H. R., Van den Bogert, C., Ruitenbeek, W., Jeneson, J. A. L., Wanders, R. J. A., Abeling, N. G. G. M., Dorland, B., Sengers, R. C. A., and Van Gennip, A. H. (1993). Pediatr. Res. 33, 412-417.PubMedGoogle Scholar
  3. Battini, R., Ferrari, S., Kaczmarek, L., Calabretta, B., Chen, S., and Baserga, R. (1987). J. Biol. Chem. 9, 4355-4359.Google Scholar
  4. Benz, R. (1994). Biochim. Biophys. Acta 1197, 167-196.PubMedGoogle Scholar
  5. Bisaccia, F., De Palma, A., and Palmieri, F. (1989). Biochim. Biophys. Acta 977, 171-176.PubMedGoogle Scholar
  6. Blachly-Dyson, E., Zambronicz, E. B., Yu, W. H., Adams, V., McCabe, E. R. B., Adelman, J., Colombini, M., and Forte, M. (1993). J. Biol. Chem. 268, 1835-1841.PubMedGoogle Scholar
  7. Blachly-Dyson, E., Baldini, A., Litt, M., McCabe, E. R. B., and Forte, M. (1994). Genomics 20, 62-67.CrossRefPubMedGoogle Scholar
  8. Brandolin, G., Le Saux, A., Trezeguet, V., Lauquin, G. J. M., and Vignais, P. V. (1993). J. Bioenerg. Biomembr. 25, 459-472.PubMedGoogle Scholar
  9. Brdiczka, D., and Wallimann, T. (1994). Mol. Cell. Biochem. 133/134, 69-83.Google Scholar
  10. Brivet, M., Slama, A., Rustin, P., Poggi, F., Boutron, A., Rabier, D., Munnich, A., Saudubray, J. M., and Legrand, A. (1997). International Congress of Inborn Errors of Metabolism, Vienna, abstract P69.Google Scholar
  11. Cassard, A. M., Bouillaud, F., Mattei, M. G., Hentz, E., Raimbault, S., Thomas, M., and Ricquier, D. (1990). J. Cell. Biochem. 43, 255-264.PubMedGoogle Scholar
  12. Coates, P. M., and Tanaka, K. (1992). J. Lipid Res. 33, 1099-1110.PubMedGoogle Scholar
  13. Cooperstein, S. J., and Lazarow, A. (1951). J. Biol. Chem. 189, 665-670.PubMedGoogle Scholar
  14. Cozens, A. L., Runswick, M. J., and Walker, J. E. (1989). J. Mol. Biol. 206, 261-280.PubMedGoogle Scholar
  15. Dolce, V., Fiermonte, G., Messina, A., and Palmieri, F. (1991). DNA Sequence 2, 133-135.PubMedGoogle Scholar
  16. Dolce, V., Iacobazzi, V., Palmieri, F., and Walker, J. E. (1994). J. Biol. Chem. 269, 10451-10460.PubMedGoogle Scholar
  17. Dolce, V., Fiermonte, G., and Palmieri, F. (1996). FEBS Lett. 399, 95-98.PubMedGoogle Scholar
  18. Ferreira, G. C., and Pedersen, P. L. (1993). J. Bioenerg. Biomembr. 25, 483-492.PubMedGoogle Scholar
  19. Garlid, K. D. (1994). J. Bioenerg. Biomembr. 26, 537-542.PubMedGoogle Scholar
  20. Ha, H., Hajek, P., Bedwell, D. M., and Burrows, P. D. (1993). J. Biol. Chem. 268, 12143-12149.PubMedGoogle Scholar
  21. Hayes, D. J., Taylor, D. J., Bore, P. J., Hilton-Jones, D., Arnold, D. L., Squier, M. V., Gent, A. E., and Radda, G. K. (1987). J. Neurol. Sci. 82, 27-39.PubMedGoogle Scholar
  22. Heisterkamp, N., Mulder, M. P., Langeveld, A., Ten Hoeve, J., Wang, Z., Roe, B. A., and Groffen, J. (1995). Genomics 29, 451-456.PubMedGoogle Scholar
  23. Houldsworth, J., and Attardi, G. (1988). Proc. Natl. Acad. Sci. USA 85, 377-381.PubMedGoogle Scholar
  24. Huizing, M., DePinto, V., Ruitenbeek, W., Trijbels, F. J. M., Van den Heuvel, L. P., and Wendel, U. (1996a). J. Bioenerg. Biomembr. 28, 109-114.PubMedGoogle Scholar
  25. Huizing, M., Ruitenbeek, W., Thinnes, F. P., DePinto, V., Wendel, U., Trijbels, J. M. F., Smit, L. M. E., Ter Laak, H. J., and Van den Heuvel, L. P. (1996b). Pediatr. Res. 39, 760-765.PubMedGoogle Scholar
  26. Huizing, M., Iacobazzi, V., IJlst, L., Savelkoul, P., Ruitenbeek, W., Van den Heuvel, L., Indiveri, C., Smeitink, J., Trijbels, F., Wanders, R., and Palmieri, F. (1997). Am. J. Hum. Genet. 61, 1239-1245.PubMedGoogle Scholar
  27. Huizing, M., Wendel, U., Ruitenbeek, W., Iacobazzi, V., IJlst, L., Veenhuizen, P. T. M., Savelkoul, P., Van den Heuvel, L. P., Smeitink, J. A. M., Wanders, R. J. A., Trijbels, F. J. M., and Palmieri, F. (1998). J. Inher. Metab. Dis., in press.Google Scholar
  28. Iacobazzi, V., Palmieri, F., Runswick, M. J., and Walker, J. E. (1992). DNA Sequence 3, 79-88.PubMedGoogle Scholar
  29. Iacobazzi, V., Lauria, G., and Palmieri, F. (1997). DNA Sequence 7, 127-139.PubMedGoogle Scholar
  30. Indiveri, C., Krämer, R., and Palmieri, F. (1987). J. Biol. Chem. 262, 15979-15983.PubMedGoogle Scholar
  31. Indiveri, C., Tonazzi, A., and Palmieri, F. (1990). Biochim. Biophys. Acta 1020, 81-86.PubMedGoogle Scholar
  32. Inoue, I., Saheki, T., Kayanuma, K., Uono, M., Nakajima, M., Takeshita, K., Koike, R., Yuasa, T., Miyatake, T., and Sakoda, K. (1988). Biochim. Biophys. Acta 964, 90-95.PubMedGoogle Scholar
  33. Jung, D. W., and Brierly, G. P. (1994). J. Bioenerg. Biomembr. 26, 527-535.PubMedGoogle Scholar
  34. Kaplan, R. S., Mayor, J. A., and Wood, D. O. (1993). J. Biol. Chem. 268, 13682-13690.PubMedGoogle Scholar
  35. Klingenberg, M. (1981). Nature 290, 449-454.PubMedGoogle Scholar
  36. Li, W., Shariat-Madar, Z., Powers, M., Sun, X., Lane, R. D., and Garlid, K. D. (1992). J. Biol. Chem. 267, 17983-17989.PubMedGoogle Scholar
  37. Mannella, C. A. (1992). Trends Biochem. Sci. 17, 315-320.PubMedGoogle Scholar
  38. Marsh, S., Carter, N. P., Dolce, V., Iacobazzi, V., and Palmieri, F. (1995). Genomics 29, 814-815.PubMedGoogle Scholar
  39. McEnery, M. W., Dawson, T. M., Verma, A., Gurley, D., Colombini, M., and Snyder, S. H. (1993). J. Biol. Chem. 268, 23289-23296.PubMedGoogle Scholar
  40. Neckelmann, N., Li, K., Wade, R. P., Shuster, R., and Wallace, D. C. (1987). Proc. Natl. Acad. Sci. USA 84, 7580-7584.PubMedGoogle Scholar
  41. Palmieri, F. (1994). FEBS Lett. 346, 48-54.PubMedGoogle Scholar
  42. Palmieri, F., Bisaccia, F., Capobianco, L., Dolce, V., Fiermonte, G., Iacobazzi, V., and Zara, V. (1993). J. Bioenerg. Biomembr. 25, 493-501.PubMedGoogle Scholar
  43. Palmieri, F., and Van Ommen, B. (1998). In Frontiers of Cellular Bioenergetics: Molecular Biology, Biochemistry and Physiopathology (Papa, S., et al., eds.), Plenum Press, New York/London, in press.Google Scholar
  44. Pande, S. V. (1975). Proc. Natl. Acad. Sci. USA 72, 883-887.PubMedGoogle Scholar
  45. Pande, S. V., and Murthy, M. S. R. (1994). Biochim. Biophys. Acta 1226, 269-276.PubMedGoogle Scholar
  46. Ramsay, R. R., and Tubbs, P. K. (1975). FEBS Lett. 54, 21-25.PubMedGoogle Scholar
  47. Ruitenbeek, W., Huizing, M., DePinto, V., Thinnes, F. P., Trijbels, J. M. F., Wendel, U., and Sengers, R. C. A. (1995). In Progress in Cell Research, Vol. V (Palmieri, F., ed.), Elsevier, Amsterdam, pp. 225-229.Google Scholar
  48. Schapira, A. H. V., Cooper, J. M., Morgan-Hughes, J. A., Landon, D. N., and Clark, J. B. (1990). N. Engl. J. Med. 323, 37-42.PubMedGoogle Scholar
  49. Schultheiss, H. P., Schulze, K., and Dörner, A. (1996). Mol. Cell. Biochem. 163/164, 319-327.Google Scholar
  50. Selak, M. A., Grover, W. D., Foley, C. M., Miles, D. K., and Salganicoff, L. (1997). International Conference on Mitochondrial Diseases, Philadelphia, abstract book (Grover, W. D., ed.), abstract 59.Google Scholar
  51. Sengers, R. C. A., Trijbels, J. M. F., Willems, J. L., Daniëls, O., and Stadhouders, A. M. (1975). J. Pediatr. 86, 873-880.PubMedGoogle Scholar
  52. Smeitink, J. A. M., Sengers, R. C. A., Trijbels, J. M. F., Ruitenbeek, W., Daniëls, O., Stadhouders, A. M., and Kock-Jansen, M. J. H. (1989). Eur. J. Pediatr. 148, 656-659.PubMedGoogle Scholar
  53. Smeitink, J., Huizing, M., Ruitenbeek, W., Van den Heuvel, B., Trijbels, F., and Sengers, R. (1997). J. Inher. Metab. Dis. 20, 7 (abstract 013).Google Scholar
  54. Stanley, C. A., Hale, D. E., Berry, G. T., DeLeeuw, S., Boxer, J., and Bonnefont, J. P. (1992). N. Engl. J. Med. 327, 19-22.PubMedGoogle Scholar
  55. Stepien, G., Torroni, A., Chung, A. B., Hodge, J. A., and Wallace, D. C. (1992). J. Biol. Chem. 267, 14592-14597.PubMedGoogle Scholar
  56. Torroni, A., Stepien, G., Hodge, J. A., and Wallace, D. C. (1990). J. Biol. Chem. 265, 20589-20593.PubMedGoogle Scholar
  57. Trijbels, J. M. F., Scholte, H. R., Ruitenbeek, W., Sengers, R. C. A., Janssen, A. J. M., and Busch, H. F. M. (1993). Eur. J. Pediatr. 152, 178-184.PubMedGoogle Scholar
  58. Viggiano, L., Iacobazzi, V., Marzella, R., Cassano, C., Rocchi, M., and Palmieri, F. (1997). Cytogenet. Cell Genet. 79, 62-63.PubMedGoogle Scholar
  59. Winkelbach, H., Walter, G., Morys-Wortmann, C., Paetzold, G., Hesse, D., Zimmermann, B., Flörke, H., Reymann, S., Stadtmüller, U., Thinnes, F. P., and Hilschmann, N. (1994). Biochem. Med. Metab. Biol. 52, 120-127.PubMedGoogle Scholar
  60. Wyss, M., Smeitink, J., Wevers, R. A., and Wallimann, T. (1992). Biochim. Biophys. Acta 1102, 119-166.PubMedGoogle Scholar
  61. Yu, W. H., Wolfgang, W., and Forte, M. (1995). J. Biol. Chem. 270, 13998-14006.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Marjan Huizing
    • 1
  • Wim Ruitenbeek
    • 1
  • Lambert P. van den Heuvel
    • 1
  • Vincenza Dolce
    • 2
  • Vito Iacobazzi
    • 2
  • Jan A. M. Smeitink
    • 1
  • Ferdinando Palmieri
    • 2
  • J. M. Frans Trijbels
    • 1
  1. 1.Department of PediatricsUniversity HospitalNijmegenThe Netherlands
  2. 2.Department of Pharmaco-BiologyUniversity of BariBariItaly

Personalised recommendations