Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Acidocalcisomes ? conserved from bacteria to man

Nature Reviews Microbiology volume 3, pages 251–261 (2005)Cite this article

Abstract

Recent work has shown that acidocalcisomes, which are electron-dense acidic organelles rich in calcium and polyphosphate, are the only organelles that have been conserved during evolution from prokaryotes to eukaryotes. Acidocalcisomes were first described in trypanosomatids and have been characterized in most detail in these species. Acidocalcisomes have been linked with several functions, including storage of cations and phosphorus, polyphosphate metabolism, calcium homeostasis, maintenance of intracellular pH homeostasis and osmoregulation. Here, we review acidocalcisome ultrastructure, composition and function in different trypanosomatids and other organisms.

Key Points

  • Acidocalcisomes are acidic and dense organelles ? both by weight and by electron microscopy ? with a high concentration of phosphorus present as pyrophosphate and polyphosphate (poly P) that is complexed with calcium, and other elements.

  • Acidocalcisomes are related to organelles previously named volutin or metachromatic granules, and polyphosphate vacuoles, which were thought to function as storage granules.

  • The acidocalcisome membrane can contain several pumps (Ca2+-ATPase, V-H+-ATPase, V-H+-PPase), exchangers (Na+/H+, Ca2+/H+), and channels (aquaporins), while its matrix contains enzymes related to pyrophosphate and polyphosphate metabolism (exopolyphosphatase, polyphosphate kinase, pyrophosphatase).

  • After their identification in trypanosomatids, acidocalcisomes were found in other microorganisms such as Toxoplasma gondii, Plasmodium spp., the green alga Chlamydomonas reinhardtii, and the slime mould Dictyostelium discoideum. The recent identification of acidocalcisomes in bacteria (Agrobacterium tumefaciens, Rhodospirillum rubrum) and the finding that human platelet dense granules are homologous to acidocalcisomes, indicates that these organelles have been conserved during evolution from bacteria to humans.

  • Acidocalcisomes have been linked with several functions, including storage of cations and phosphorus, polyphosphate metabolism, calcium homeostasis, maintenance of intracellular pH homeostasis, and osmoregulation. This review describes acidocalcisome ultrastructure, composition and function in different trypanosomatids with an overview of our knowledge of the organelle in other organisms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic representation of trypanosomatids.
Figure 2: Thin sections of acidocalcisomes of trypanosomatid parasites prepared by different transmission electron microscopy methods and of hydrogenosomes of Tritrichomonas foetus.
Figure 3: Morphology of acidocalcisomes in whole trypanosomatids.
Figure 4: Schematic representation of a typical acidocalcisome.

Similar content being viewed by others

References

  1. Urbina, J. A. & Docampo, R. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol. 19, 495–501 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Croft, S. L. & Coombs, G. H. Leishmaniasis ? current chemotherapy and recent advances in the search for new drugs. Trends Parasitol. 19, 502–508 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Fairlamb, A. Chemotherapy of human African trypanosomiasis: current and future prospects. Trends Parasitol. 19, 488–494 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Camargo, E. P. Phytomonas and other trypanosomatid parasites of plants and fruits. Adv. Parasitol. 42, 29–112 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Vercesi, A. E., Moreno, S. N. J. & Docampo, R. Ca2+/H+ exchange in acidic vacuoles of Trypanosoma brucei. Biochem. J. 304, 227–233 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Docampo, R., Scott, D. A., Vercesi, A. E. & Moreno, S. N. J. Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi. Biochem. J. 310, 1005–1012 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Docampo, R. & Moreno, S. N. J. Acidocalcisome: a novel Ca2+ storage compartment in trypanosomatids and apicomplexan parasites. Parasitol. Today 15, 443–448 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Meyer, A. Orientierende untersuchungen über verbreitung. Morphologie, und chemie des volutins. Bot. Zeit. 62, 113–152 (1904).

    Google Scholar 

  9. Kornberg, A. Inorganic polyphosphate: toward making a forgotten polymer unforgettable. J. Bacteriol. 177, 491–496 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jensen, T. E. in Ultrastructure of Microalgae (ed. Berner, T.) 7–50 (CRC Press, Boca Raton, Florida, 1993).

    Google Scholar 

  11. Moreno, S. N. J. & Zhong, L. Acidocalcisomes in Toxoplasma gondii tachyzoites. Biochem. J. 313, 655–659 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Garcia, C. R. et al. Acidic calcium pools in intraerythrocytic malaria parasites. Eur. J. Cell Biol. 76, 133–138 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Luo, S., Marchesini, N., Moreno, S. N. J. & Docampo, R. A plant-like vacuolar H+-pyrophosphatase in Plasmodium falciparum. FEBS Lett. 460, 217–220 (1999).

    Article  CAS  PubMed  Google Scholar 

  14. Marchesini, N., Luo, S., Rodrigues, C. O., Moreno, S. N. J. & Docampo, R. Acidocalcisomes and a vacuolar H+-pyrophosphatase in malaria parasites. Biochem. J. 347, 243–253 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ruiz, F. A., Marchesini, N., Seufferheld, M., Govindjee & Docampo, R. The polyphosphate bodies of Chlamydomonas reinhardtii possess a proton pumping pyrophosphatase and are similar to acidocalcisomes. J. Biol. Chem. 276, 46196–46203 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Marchesini, N., Ruiz, F. A., Vieira, M. & Docampo, R. Acidocalcisomes are functionally linked to the contractile vacuole of Dictyostelium discoideum. J. Biol. Chem. 277, 8146–8153 (2002).

    Article  CAS  PubMed  Google Scholar 

  17. Seufferheld, M. et al. Identification in bacteria of organelles similar to acidocalcisomes of unicellular eukaryotes. J. Biol. Chem. 278, 29971–29978 (2003). First report of membrane-bound acidocalcisomes in bacteria, which were identified by X-ray microanalysis, subcellular fractionation and fluorescence and electron microscopy.

    Article  CAS  PubMed  Google Scholar 

  18. Seufferheld, M., Lea, C. R., Vieira, M., Oldfield, E. & Docampo, R. The H+-pyrophosphatase of Rhodospirillum rubrum is predominantly located in polyphosphate-rich acidocalcisomes. J. Biol. Chem. 279, 51193–51202 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Ruiz, F. A., Lea, C. R., Oldfield, E. & Docampo, R. Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J. Biol. Chem. 279, 44250–44267 (2004). Shows that human platelet dense granules have morphological and structural similarities to acidocalcisomes, and contain polyphosphate that was released on thrombin stimulation.

    Article  CAS  PubMed  Google Scholar 

  20. Scott, D. A. & Docampo, R. Characterization of isolated acidocalcisomes of Trypanosoma cruzi. J. Biol. Chem. 275, 24215–22421 (2000). The purification method of acidocalcisomes using iodixanol gradient centrifugation was developed.

    Article  CAS  PubMed  Google Scholar 

  21. De Souza, W. Basic cell biology of Trypanosoma cruzi. Curr. Pharm. Design 8, 269–285 (2002).

    Article  CAS  Google Scholar 

  22. Miranda, K. et al. Acidocalcisomes of Phytomonas françai possess distinct morphological characteristics and contain iron. Microsc. Microanal. 10, 647–655 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Lu, H. -G. et al. Ca2+ content and expression of an acidocalcisomal calcium pump are elevated in intracellular forms of Trypanosoma cruzi. Mol. Cell. Biol. 18, 2309–2323 (1998). First report of a PMCA-type Ca2+-ATPase in acidocalcisomes. The gene was cloned, sequenced, expressed and shown to complement yeast deficient in PMC1 , and the protein was shown to localize in acidocalcisomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Miranda, K., Benchimol, M., Docampo, R. & de Souza, W. The fine structure of acidocalcisomes of Trypanosoma cruzi. Parasitol. Res. 86, 373–384 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Scott, D. A., Docampo, R., Dvorak, J. A., Shi, S. & Leapman, R. D. In situ compositional analysis of acidocalcisomes of Trypanosoma cruzi. J. Biol Chem. 272, 28020–28029 (1997). Quantitative analysis of the elemental composition of acidocalcisomes. On the basis of the response to ionophores it was established that acidocalcisomes correspond to the electron-dense organelles previously identified in trypanosomes.

    Article  CAS  PubMed  Google Scholar 

  26. Miranda, K. et al. Dynamics of polymorphism of acidocalcisomes in Leishmania parasites. Histochem. Cell Biol. 121, 407–418 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. Miranda, K., Docampo, R., Grillo, O. & de Souza, W. Acidocalcisomes of trypanosomatids have species-specific elemental composition. Protist 155, 395–405 (2004).

    Article  CAS  PubMed  Google Scholar 

  28. Rodrigues, C. O., Scott, D. A. & Docampo, R. Characterization of a vacuolar pyrophosphatase in Trypanosoma brucei and its localization to acidocalcisomes. Mol. Cell. Biol. 19, 7712–7723 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ruiz, F. A., Luo, S., Moreno, S. N. J. & Docampo, R. Polyphosphate content and fine structure of acidocalcisomes of Plasmodium falciparum. Microsc. Microanal. 10, 563–567 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Montalvetti, A., Rohloff, P. & Docampo, R. A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi. J. Biol. Chem. 279, 38673–38682 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Luo, S., Rohloff, P., Cox, J., Uyemura, S. A. & Docampo, R. Trypanosoma brucei plasma membrane-type Ca2+-ATPase 1 (TbPMC1) and 2 (TbPMC2) genes encode functional Ca2+-ATPases localized to the acidocalcisomes and plasma membrane, and essential for Ca2+ homeostasis and growth. J. Biol. Chem. 279, 14427–14439 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Luo, S., Vieira, M., Graves, J., Zhong, L. & Moreno, S. N. J. A plasma membrane-type Ca2+-ATPase co-localizes with a vacuolar H+-pyrophosphatase to acidocalcisomes of Toxoplasma gondii. EMBO J. 20, 55–64 (2001). Identification of a Ca2+-ATPase and its co-localization with the V-H+-PPase in acidocalcisomes of T. gondii.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moniakis, J., Coukell, M. B. & Forer, A. Molecular cloning of an intracellular P-type ATPase from Dictyostelium that is up-regulated in calcium-adapted cells. J. Biol. Chem. 270, 28276–29281 (1995).

    Article  CAS  PubMed  Google Scholar 

  34. Cunningham, K. W. & Fink, G. R. Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases. J. Cell Biol. 124, 351–363 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Ghosh, S. K., Rosenthal, B., Rogers, R. & Samuelson, J. Vacuolar localization of an Entamoeba histolytica homologue of the plasma membrane ATPase (PMCA). Mol. Biochem. Parasitol. 108, 125–130 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Bowman, E. J., Siebers, A. & Altendorf, K. Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc. Natl Acad. Sci. USA 85, 7972–7976 (1988).

    Article  CAS  PubMed  Google Scholar 

  37. Scott, D. A., Moreno, S. N. J. & Docampo, R. Ca2+ storage in Trypanosoma brucei: the influence of cytoplasmic pH and importance of vacuolar acidity. Biochem. J. 310, 789–794 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lu, H. -G. et al. Intracellular Ca2+ pool content and signaling and expression of a calcium pump are linked to virulence in Leishmania mexicana amazonensis J. Biol. Chem. 272, 9464–9473 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Mendoza, M. et al. Physiological and morphological evidences for the presence of acidocalcisomes in Trypanosoma evansi: single cell fluorescence and 31P NMR studies. Mol. Biochem. Parasitol. 125, 23–33 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Benchimol, M. et al. Functional expression of a vacuolar-type H+-ATPase in the plasma membrane and intracellular vacuoles of Trypanosoma cruzi. Biochem. J. 332, 695–702 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Scott, D. A. et al. Presence of a plant-like proton-pumping pyrophosphatase in acidocalcisomes of Trypanosoma cruzi. J. Biol. Chem. 273, 22151–22158 (1998). First report and biochemical characterization of a V-H+-PPase in a unicellular eukaryotic parasite.

    Article  CAS  PubMed  Google Scholar 

  42. Lemercier, G. et al. A vacuolar-type H+ pyrophosphatase governs maintenance of functional acidocalcisomes and growth of the insect and bloodstream forms of Trypanosoma brucei. J. Biol. Chem. 277, 37369–37376 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Rodrigues, C. O., Scott, D. A. & Docampo, R. Presence of a vacuolar H+-pyrophosphatase in promastigotes of Leishmania donovani and its localization to a different compartment from the vacuolar H+-ATPase. Biochem J. 340, 759–766 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rodrigues, C. O. et al. Vacuolar proton pyrophosphatase activity and pyrophosphate (PPi) in Toxoplasma gondii as possible chemotherapeutic targets. Biochem. J. 349, 737–745 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hill, J., Scott, D. A., Luo, S. & Docampo, R. Cloning and functional expression of a gene encoding a vacuolar-type proton-translocating pyrophosphatase from Trypanosoma cruzi. Biochem. J. 351, 281–288 (2000). First cloning and functional expression of a V-H+-PPase from an organism that is neither a bacteria or plant.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rodrigues, C. O., Ruiz, F. A., Rohloff, P., Scott, D. A. & Moreno, S. N. J. Characterization of isolated acidocalcisomes from Toxoplasma gondii tachyzoites reveals a novel pool of hydrolysable polyphosphate. J. Biol. Chem. 277, 48650–48656 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Martinez, R. et al. A proton pumping pyrophosphatase in the Golgi apparatus and plasma membrane vesicles of Trypanosoma cruzi. Mol. Biochem. Parasitol. 120, 205–213 (2002).

    Article  CAS  PubMed  Google Scholar 

  48. Vercesi, A. E. & Docampo, R. Sodium-proton exchange stimulates Ca2+ release from acidocalcisomes of Trypanosoma brucei. Biochem. J. 315, 265–270 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Vercesi, A. E., Grijalba, M. T. & Docampo, R. Inhibition of Ca2+ release from Trypanosoma brucei acidocalcisomes by 3,5-dibutyl-4-hydroxytoluene (BHT): role of the Na+/H+ exchange. Biochem. J. 328, 479–482 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vercesi, A. E., Rodrigues, C. O., Catisti, R. & Docampo, R. Presence of a Na+/H+ exchanger in acidocalcisomes of Leishmania donovani and their alkalization by anti-leishmanial agents. FEBS Lett. 473, 203–206 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Moreno, S. N. J., Docampo, R. & Vercesi, A. E. Calcium homeostasis in procyclic and bloodstream forms of Trypanosoma brucei. Lack of inositol 1,4,5-trisphosphate-sensitive Ca2+ release. J. Biol. Chem. 267, 6020–6026 (1992).

    CAS  PubMed  Google Scholar 

  52. Moreno, S. N. J., Vercesi, A. E., Pignataro, O. P. & Docampo, R. Calcium homeostasis in Trypanosoma cruzi amastigotes. Presence of inositol phosphates and lack of an inositol 1,4,5-trisphosphate-sensitive calcium pool. Mol. Biochem. Parasitol. 52, 251–262 (1992).

    Article  CAS  PubMed  Google Scholar 

  53. Docampo, R., Moreno, S. N. J. & Vercesi, A. E. Effect of thapsigargin on calcium homeostasis in Trypanosoma cruzi trypomastigotes and epimastigotes. Mol. Biochem. Parasitol. 59, 305–314 (1993).

    Article  CAS  PubMed  Google Scholar 

  54. Urbina, J. A. et al. Trypanosoma cruzi contains major pyrophosphate stores and its growth in vitro and in vivo is blocked by pyrophosphate analogs. J. Biol. Chem. 274, 33609–33615 (1999). Pyrophosphate is found in trypanosomes at greater concentrations than ATP and localized in acidocalcisomes, which establishes pyrophosphate metabolism as a therapeutic target.

    Article  CAS  PubMed  Google Scholar 

  55. Dvorak, J. A., Engel, J. C., Leapman, R. D., Swyt, C. R. & Pella, P. A. Trypanosoma cruzi: elemental composition hetereogeneity of cloned stocks. Mol. Biochem. Parasitol. 31, 19–26 (1988).

    Article  CAS  PubMed  Google Scholar 

  56. LeFurgey, A., Ingram, P. & Blum, J. J. Elemental composition of polyphosphate-containing vacuoles and cytoplasm of Leishmania major. Mol. Biochem. Parasitol. 40, 77–86 (1990).

    Article  CAS  PubMed  Google Scholar 

  57. LeFurgey, A., Ingram, P. & Blum, J. J. Compartmental responses to acute osmotic stress in Leishmania major result in rapid loss of Na+ and Cl−. Comp. Biochem. Physiol. Mol. Integr. Physiol. 128, 385–394 (2001).

    Article  CAS  Google Scholar 

  58. Correa, A. F., Andrade, L. R. & Soares., M. J. Elemental composition of acidocalcisomes of Trypanosoma cruzi bloodstream trypomastigote forms. Parasitol Res. 88, 875–880 (2002).

    Article  PubMed  Google Scholar 

  59. Moreno, B. et al. 31P NMR spectroscopy of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major: Evidence for high levels of condensed inorganic phosphates. J. Biol. Chem. 275, 28356–28362 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Ruiz, F. A., Rodrigues, C. O. & Docampo, R. Rapid changes in polyphosphate content within acidocalcisomes in response to cell growth, differentiation, and environmental stress in Trypanosoma cruzi. J. Biol. Chem. 276, 26114–26121 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Moreno, B. et al. Magic-angle spinning 31P NMR spectroscopy of condensed phosphates in parasitic protozoa: visualizing the invisible. FEBS Lett. 523, 207–212 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Rohloff, P., Rodrigues, C. O. & Docampo, R. Regulatory volume decrease in Trypanosoma cruzi involves amino acid efflux and changes in intracellular calcium. Mol. Biochem. Parasitol. 126, 219–230 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Rodrigues, C. O., Ruiz, F. A., Vieira, M., Hill, J. E. & Docampo, R. An acidocalcisomal exopolyphosphatase from Leishmania major with higher affinity for short-term polyphosphate. J. Biol. Chem. 277, 50899–50906 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. Lemercier, G. et al. A pyrophosphatase regulating polyphosphate metabolism in acidocalcisomes is essential for Trypanosoma brucei virulence in mice. J. Biol. Chem. 279, 3420–3425 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Xiong, Z. -H., Ridgley, E. L., Enis, D., Olness, F. & Ruben, L. Selective transfer of calcium from an acidic compartment to the mitochondrion of Trypanosoma brucei: measurements with targeted aequorin. J. Biol. Chem. 272, 31022–31028 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. Rohloff, P., Montalvetti, A. & Docampo, R. Acidocalcisomes and the contractile vacuole complex are involved in osmoregulation in Trypanosoma cruzi. J. Biol. Chem. 279, 52270–52281 (2004). The role of acidocalcisomes and the contractile vacuole of trypanosomes in osmoregulation is shown.

    Article  CAS  PubMed  Google Scholar 

  67. Bringaud, F., Baltz, D. & Baltz, T. Functional and molecular characterization of a glycosomal PPi-dependent enzyme in trypanosomatids: pyruvate, phosphate dikinase. Proc. Natl Acad. Sci. USA 95, 7963–7968 (1998).

    Article  CAS  PubMed  Google Scholar 

  68. Ho, A. M., Johnson, M. D. & Kingsley, D. M. Role of the mouse ank gene in control of tissue calcification and arthritis. Science 289, 265–270 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Wadsworth, S. J. & Van Rossum, G. D. V. Role of vacuolar adenosine triphosphate in the regulation of cytosolic pH in hepatocytes. J. Membrane Biol. 142, 21–34 (1994).

    Article  CAS  Google Scholar 

  70. Bronk, S. F. & Gores, G. J. Efflux of protons from acidic vesicles contributes to cytosolic acidification of hepatocytes during ATP depletion. Hepatology 14, 626–633 (1991).

    Article  CAS  PubMed  Google Scholar 

  71. Madshus, I. H., Tonnessen, T. I., Olsnes, S. & Sandvig, K. Effect of potassium depletion of Hep 2 cells on intracellular pH and on chloride uptake by anion antiport. J. Cell Physiol. 131, 6–13 (1987).

    Article  CAS  PubMed  Google Scholar 

  72. Castro, C. D., Koretsky, A. P. & Domach, M. M. NMR-observed phosphate trafficking and polyphosphate dynamics in wild-type and vph1-1 mutant Saccharomyces cerevisiae in response to stresses. Biotechnol. Prog. 15, 65–73 (1999).

    Article  Google Scholar 

  73. Allen, R. D. & Naitoh, Y. Osmoregulation and contractile vacuoles of protozoa. Int. Rev. Cytol. 215, 351–394 (2002).

    Article  CAS  PubMed  Google Scholar 

  74. Clark, T. B. Comparative morphology of four genera of trypanosomatidae. J. Protozool. 6, 227–232 (1959).

    Article  Google Scholar 

  75. Linder, J. C. & Staehelin, L. A. A novel model for fluid secretion by the trypanosomatid contractile vacuole apparatus. J. Cell Biol. 83, 371–382 (1979).

    Article  CAS  PubMed  Google Scholar 

  76. Attias, M., Vommaro, R. C. & de Souza, W. Computer aided three-dimensional reconstruction of the free-living protozoan Bodo sp. (Kinetoplastida:Bodonidae). Cell Struct. Funct. 21, 297–306 (1996).

    Article  CAS  PubMed  Google Scholar 

  77. McConville, M. J., Mullin, K. A., Ilgoutz, S. C. & Teasdale, R. D. Secretory pathway of trypanosomatid parasites. Microbiol. Mol. Biol. Rev. 66, 122–154 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Morgan, G. W., Hall, B. S., Denny, P. W., Field, M. C. & Carrington, M. The endocytic apparatus of the kinetoplastida. Part II: machinery and components of the system. Trends Parasitol. 118, 540–546 (2002).

    Article  Google Scholar 

  79. Docampo, R. & Moreno, S. N. J. (2001) The acidocalcisome. Mol. Biochem. Parasitol. 114, 151–159.

    Article  CAS  PubMed  Google Scholar 

  80. Drozdowicz, Y. M. et al. Isolation and characterization of TgVP1, a type I vacuolar H+-translocating pyrophosphatase from Toxoplasma gondii. The dynamics of its subcellular localization and the cellular effects of a diphosphonate inhibitor. J. Biol. Chem. 278, 1075–1085 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Dutoya, S. et al. A novel C-terminal kinesin is essential for maintaining functional acidocalcisomes in Trypanosoma brucei. J. Biol. Chem. 276, 49117–49124 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Zhang, K. et al. Leishmania salvage of host sphingolipids accompanied by remodeling to form parasite-specific inositol phosphoceramide is required for acidocalcisome biogenesis and parasite survival. Mol. Microbiol. (in the press). A role for sphingolipid biosynthesis in acidocalcisome biogenesis is established.

  83. Saliba, K. J. et al. Acidification of the malaria parasite's digestive vacuole by a H+-ATPase and a H+-pyrophosphatase. J. Biol. Chem. 278, 5605–5612 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Biagini, G., Bray, P. G., Spiller, D. G., White, M. R. H. & Ward, S. A. The digestive food vacuole of the malaria parasite is a dynamic intracellular Ca2+ store. J. Biol. Chem. 278, 27910–27915 (2003).

    Article  CAS  PubMed  Google Scholar 

  85. Maeshima, M. Tonoplast transporters: organization and function. Annu. Rev. Plant Physiol. 52, 469–497 (2001).

    Article  CAS  Google Scholar 

  86. Lindmark, D. G. & Müller, M. Hydrogenosome, a cytoplasmic organelle of the anaerobic flagellate Tritrichomonas foetus, and its role in pyruvate metabolism. J. Biol. Chem. 248, 7724–7728 (1973).

    CAS  PubMed  Google Scholar 

  87. Bui, E. T., Bradley, P. J. & Johnson, P. J. A common evolutionary origin for mitochondria and hydrogenosomes. Proc. Natl Acad. Sci. USA 93, 9651–9656 (1996).

    Article  CAS  PubMed  Google Scholar 

  88. Dyall, S. D. & Johnson, P. J. Origins of hydrogenosomes and mitochondria. Evolution and organelle biogenesis. Curr. Opin. Microbiol. 3, 404–411 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Ribeiro, K. C., Benchimol, M. & Farina, M. Contribution of cryofixation and freeze-substitution to analytical microscopy: a study of Tritrichomonas foetus hydrogenosomes. Microsci. Res. Tech. 53, 87–92 (2001).

    Article  CAS  Google Scholar 

  90. Benchimol, M., Aquino Almeida, J. C., Lins, U., Rodrigues Gonçalves, N. & de Souza, W. Electron microscopy study of the effect of Zn on Tritrichomonas foetus. Antimicrob. Agents Chemother. 37, 2722–2726 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Biagini, G. A., van der Giezen, M., Hill, B., Winters, C. & Lloyd, D. Ca2+ accumulation in the hydrogenosomes of Neocallimastix frontalis L2: a mitochondrial-like physiological role. FEMS Microbiol Lett. 149, 227–232 (1997).

    Article  CAS  Google Scholar 

  92. Jiang, L. et al. The protein storage vacuole: a unique compound organelle. J. Cell Biol. 155, 991–1002 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Ferguson, M. A. J., Haldar, K. & Cross, G. A. M. Trypanosoma brucei variant surface glycoprotein has a sn-1,2-dimyristoylglycerol membrane anchor at its COOH terminus. J. Biol Chem. 260, 4963–4968 (1985).

    CAS  PubMed  Google Scholar 

  94. Ferguson, M. A. J. The structure, biosynthesis and functions of glycosylphosphatidylinositol, and the contributions of trypanosome research. J. Cell Sci. 112, 2799–2809 (1999).

    CAS  PubMed  Google Scholar 

  95. Gull, K. The cytoskeleton of trypanosomatid parasites. Annu. Rev. Microbiol. 53, 629–655 (1999).

    Article  CAS  PubMed  Google Scholar 

  96. Moreira-Leite, F. F., Sherwin, T., Kohl, L. & Gull, K. A trypanosome structure involved in transmitting cytoplasmic information during cell division. Science 294, 610–612 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Ziemann, H. Eine methode der doppelfärbung bei flagellaten, pilzen, spirillen und bakterien, sowie bei einigen amöben. Zentralbl. Bakteriol. Parasitenkd. Infektionskr. Hyg. 24, 945–955 (1898).

    Google Scholar 

  98. Shapiro, T. A. & Englund, P. The structure and replication of kinetoplast DNA. Annu. Rev. Microbiol. 49, 117–143 (1995).

    Article  CAS  PubMed  Google Scholar 

  99. Benne, R. et al. Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46, 819–826 (1986).

    Article  CAS  PubMed  Google Scholar 

  100. Blum, B., Bakalara, N. & Simpson, L. A model for RNA editing in kinetoplastid mitochondria: 'guide' RNA molecules transcribed from maxicircle DNA provide the edited information. Cell 60, 189–198 (1990).

    Article  CAS  PubMed  Google Scholar 

  101. Boothroyd, J. C. & Cross, G. A. M. Transcripts encoding for variant surface glycoproteins of Trypanosoma brucei have a short, identical exon at their 5′ end. Gene 20, 281–289 (1982).

    Article  CAS  PubMed  Google Scholar 

  102. Liang, X. -H., Haritan, A., Uliel, S. & Michaeli, S. Trans and cis splicing in trypanosomatids: mechanism, factors, and regulation. Eukaryot. Cell 2, 830–840 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Opperdoes, F. R. & Borst, P. Localization of nine glycolytic enzymes in a microbody-like organelle in Trypanosoma brucei: the glycosome. FEBS Lett. 80, 360–364 (1977).

    Article  CAS  PubMed  Google Scholar 

  104. Parsons, M. Glycosomes: parasites and the divergence of peroxisomal function. Mol. Microbiol. 53, 717–724 (2004).

    Article  CAS  PubMed  Google Scholar 

  105. Fairlamb, A. H., Blackburn, P., Ulrich, P., Chait, B. T. & Cerami, A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 227, 1485–1487 (1985).

    Article  CAS  PubMed  Google Scholar 

  106. Muller, S., Liebau, E., Walter, R. D. & Krauth-Siegel, R. L. Thiol-based redox metabolism of protozoan parasites. Trends Parasitol. 19, 320–328 (2003).

    Article  CAS  PubMed  Google Scholar 

  107. Kornberg, A., Rao, N. N., & Ault-Riché, D. Inorganic polyphosphate: a molecule of many functions. Annu. Rev. Biochem. 68, 89–125 (1999).

    Article  CAS  PubMed  Google Scholar 

  108. Kulaev, I. & Kulakovskaya, T. Polyphosphate and phosphate pump. Annu. Rev. Microbiol. 54, 709–734 (2000).

    Article  CAS  PubMed  Google Scholar 

  109. Chapman, A. G. & Atkinson, D. E. Adenine nucleotide concentrations and turnover rates. Their correlation with biological activity in bacteria and yeast. Adv. Microbiol. Physiol. 15, 253–306 (1977).

    Article  CAS  Google Scholar 

  110. Rao, N. N. & Kornberg, A. Inorganic polyphosphate supports resistance and survival of stationary-phase Escherichia coli. J. Bacteriol. 178, 1394–1400 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Castro, C. D., Meehan, A. J., Koretsky, A. P. & Domach, M. M. In situ31P nuclear magnetic resonance for observation of polyphosphate and catabolite responses of chemostat-cultivated Saccharomyces cerevisiae after alkalinization. Appl. Environ. Microbiol. 61, 4448–4453 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Yang, Y. C., Bastos, M. & Chen, K. Y. Effects of osmotic stress and growth stage on cellular pH and polyphosphate metabolism in Neurospora crassa as studied by 31P nuclear magnetic resonance spectroscopy. Biochim. Biophys. Acta 1179, 141–147 (1993).

    Article  CAS  PubMed  Google Scholar 

  113. Pick, U. & Weiss, M. Polyphosphate hydrolysis within acidic vacuoles in response to amine-induced alkaline stress in the halotolerant alga Dunaliella salina. Plant Physiol. 97, 1234–1240 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Weiss, M., Bental, M. & Pick, U. Hydrolysis of polyphosphates and permeability changes in response to osmotic shocks in cells of the halotelerant alga Dunaliella. Plant Physiol. 97, 1241–1248 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Pick, U., Zeelon, O. & Weiss, M. Amine accumulation in acidic vacuoles protects the halotolerant alga Dunaliella salina against alkaline stress. Plant Physiol. 97, 1226–1233 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Wurts, H., Shiba, T. & Kornberg, A. The gene for a major exopolyphosphatase of Saccharomyces cerevisiae. J. Bacteriol. 177, 898–906 (1995).

    Article  Google Scholar 

  117. Sethuraman, A., Rao, N. N. & Kornberg, A. The endopolyphosphatase gene: essential in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 98, 8542–8547 (2001).

    Article  CAS  PubMed  Google Scholar 

  118. Kornberg, A. Biochemistry matters. Nature Struct. Mol. Biol. 6, 493 (2004).

    Article  CAS  Google Scholar 

  119. Gomez-Garcia, M. R. & Kornberg, A. Formation of an actin-like filament concurrent with the enzymatic synthesis of inorganic polyphosphate. Proc. Natl Acad. Sci. USA 101, 15876–15880 (2004). A polyphosphate kinase of possible acidocalcisome localization is identified as a complex of actin-related proteins.

    Article  CAS  PubMed  Google Scholar 

  120. Leon, G. et al. Electron probe analysis and biochemical characterization of electron-dense granules secreted by Entamoeba histolytica. Mol. Biochem. Parasitol. 85, 233–242 (1997).

    Article  CAS  PubMed  Google Scholar 

  121. Mortara, R. Studies on trypanosomatid actin. I. Immunochemical and biochemical identification. J. Protozool. 36, 8–13 (1989).

    Article  CAS  PubMed  Google Scholar 

  122. Babes, V. Beobachtungen über die metachromatischen körperchen, sporenbildung, verzwiegung, kolben- und kapsel-bildung pathogener bakterien. Zentralbl. Bakteriol. Parasitenkd. Infektionskr. Hyg. 20, 412–420 (1895).

    Google Scholar 

  123. Grimme, A. Die wichtigsten methoden der bakterenfärbung in ihrer wirkung auf die membran, den protoplasten und die einschlüsse der bakterienzelle. Zentralbl. Bakteriol. Parasitenkd. Infektionskr. Hyg. 32, 161–165 (1902).

    Google Scholar 

  124. Kunze, W. Uber Orcheobius herpobdellae schuberg et kunze. Arch. Protistenk. 9, 382–390 (1907).

    Google Scholar 

  125. Swellengrebel, N. H. La volutine chez les trypanosomes. C. R. Soc. Biol. Paris 64, 38–43 (1908).

    Google Scholar 

  126. Erdnmann, R. Kern und metachromatische körper bei sarkosporidien. Arch. Protistenk. 20, 239–243 (1910).

    Google Scholar 

  127. Wiame, J. H. Etude d'une substance polyphosphorée, basophile et métachromatique chez les levures. Biochim. Biophys. Acta 1, 234–255 (1947)

    Article  CAS  Google Scholar 

  128. Ebel, J. P. Recherches sur les polyphosphates contenus dans diverses cellules vivantes. II. Etude chromatographique et potentiométrique des polyphosphates de levure. Bull. Soc. Chim. Biol. 34, 330 (1952).

    CAS  PubMed  Google Scholar 

  129. Vickerman, K. & Tetley, L. Recent ultrastructural studies on trypanosomes. Ann. Soc. Belge Méd. Trop. 57, 441–455 (1977).

    CAS  Google Scholar 

  130. Benchimol, M. & de Souza, W. Fine structure and cytochemistry of the hydrogenosome of Tritrichomonas foetus. J. Protozool. 30, 422–425 (1983).

    Article  CAS  PubMed  Google Scholar 

  131. de Souza, W. et al. Two special organelles found in Trypanosoma cruzi. An. Acad. Bras. Ciênc. 72, 421–432 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Work in our laboratories was funded by the US National Institutes of Health (to R.D. and S.N.J.M.), the Burroughs Wellcome Fund (to R.D. and S.N.J.M.) and Programa de Núcleos de Excelência (to W.S.).

Author information

Authors and Affiliations

  1. Department of Cellular Biology and Center for Tropical and Global Emerging Diseases, University of Georgia, Athens, 30602, Georgia, USA

    Roberto Docampo & Silvia N. J. Moreno

  2. Department of Pathobiology and Center for Zoonoses Research, University of Illinois at Urbana-Champaign, Urbana, 61802, Illinois, USA

    Roberto Docampo, Peter Rohloff & Silvia N. J. Moreno

  3. Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Wanderley de Souza & Kildare Miranda

  4. Laboratório de Biologia Celular e Tecidual da Universidade Estadual do Norte Fluminense, Campos, Brazil

    Kildare Miranda

Authors
  1. Roberto Docampo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanderley de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kildare Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Rohloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvia N. J. Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Docampo.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez

Agrobacterium tumefaciens

Chlamydomonas reinhardtii

Dictyostelium discoideum

Plasmodium falciparum

Rhodospirillum rubrum

SwissProt

TbKIFC1

FURTHER INFORMATION

Roberto Docampo and Silvia Moreno's laboratories

Glossary

AXONEME

A cytoskeletal structure of microtubules that forms flagella and cilia.

CYTOSTOME

An invagination of the plasma membrane that is used to incorporate external material.

MORPHOMETRIC STUDY

The diameter of acidocalcisomes in electron microscopy sections is measured and their volume is calculated assuming that they are perfect spheres.

DIGENETIC TRYPANOSOMATIDS

Trypanosomes that have two hosts, in contrast to monogenetic trypanosomatids which only have one host.

SPONGIOME

Tubules and vacuoles that are connected to the contractile vacuole.

PULSATION PERIOD

The period of time between contractions of the contractile vacuole.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Docampo, R., de Souza, W., Miranda, K. et al. Acidocalcisomes ? conserved from bacteria to man. Nat Rev Microbiol 3, 251–261 (2005). https://doi.org/10.1038/nrmicro1097

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro1097

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing