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A comparative assessment of mitochondrial function in epimastigotes and bloodstream trypomastigotes of Trypanosoma cruzi

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Abstract

Trypanosoma cruzi is a hemoflagellate protozoan that causes Chagas’ disease. The life cycle of T. cruzi is complex and involves different evolutive forms that have to encounter different environmental conditions provided by the host. Herein, we performed a functional assessment of mitochondrial metabolism in the following two distinct evolutive forms of T. cruzi: the insect stage epimastigote and the freshly isolated bloodstream trypomastigote. We observed that in comparison to epimastigotes, bloodstream trypomastigotes facilitate the entry of electrons into the electron transport chain by increasing complex II-III activity. Interestingly, cytochrome c oxidase (CCO) activity and the expression of CCO subunit IV were reduced in bloodstream forms, creating an “electron bottleneck” that favored an increase in electron leakage and H2O2 formation. We propose that the oxidative preconditioning provided by this mechanism confers protection to bloodstream trypomastigotes against the host immune system. In this scenario, mitochondrial remodeling during the T. cruzi life cycle may represent a key metabolic adaptation for parasite survival in different hosts.

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References

  • Adroher FJ, Osuna A, Lupianez JA (1988) Differential energetic metabolism during Trypanosoma cruzi differentiation. I. Citrate synthase, NADP-isocitrate dehydrogenase, and succinate dehydrogenase. Arch Biochem Biophys 267(1):252–261

    Article  CAS  Google Scholar 

  • Affranchino JL, Schwarcz de Tarlovsky MN, Stoppani AO (1986) Terminal oxidases in the trypanosomatid Trypanosoma cruzi. Comp Biochem Physiol B 85(2):381–388

    Article  CAS  Google Scholar 

  • Alvarez MN, Peluffo G, Piacenza L, Radi R (2011) Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: consequences for oxidative killing and role of microbial peroxiredoxins in infectivity. J Biol Chem 286(8):6627–6640

    Article  CAS  Google Scholar 

  • Atwood JA 3rd, Weatherly DB, Minning TA, Bundy B, Cavola C, Opperdoes FR et al (2005) The Trypanosoma cruzi proteome. Science 309(5733):473–476

    Article  CAS  Google Scholar 

  • Batista M, Marchini FK, Celedon PA, Fragoso SP, Probst CM, Preti H et al (2010) A high-throughput cloning system for reverse genetics in Trypanosoma cruzi. BMC Microbiol 10:259

    Article  Google Scholar 

  • Bienen EJ, Webster P, Fish WR (1991) Trypanosoma (Nannomonas) congolense: changes in respiratory metabolism during the life cycle. Exp Parasitol 73(4):403–412

    Article  CAS  Google Scholar 

  • Billingsley PF (1988) Morphometric analysis of Rhodnius prolixus Stal (Hemiptera:Reduviidae) midgut cells during blood digestion. Tissue & Cell 20(2):291–301

    Article  CAS  Google Scholar 

  • Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochemical Journal 134(3):707–716

    CAS  Google Scholar 

  • Boveris A, Stoppani AO (1977) Hydrogen peroxide generation in Trypanosoma cruzi. Experientia 33(10):1306–1308

    Article  CAS  Google Scholar 

  • Bringaud F, Riviere L, Coustou V (2006) Energy metabolism of trypanosomatids: adaptation to available carbon sources. Mol Biochem Parasitol 149(1):1–9

    Article  CAS  Google Scholar 

  • Brookes PS, Levonen AL, Shiva S, Sarti P, Darley-Usmar VM (2002) Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radic Biol Med 33(6):755–764

    Article  CAS  Google Scholar 

  • Carranza JC, Kowaltowski AJ, Mendonca MA, de Oliveira TC, Gadelha FR, Zingales B (2009) Mitochondrial bioenergetics and redox state are unaltered in Trypanosoma cruzi isolates with compromised mitochondrial complex I subunit genes. J Bioenerg Biomembr 41(3):299–308

    Article  Google Scholar 

  • Cazzulo JJ (1994) Intermediate metabolism in Trypanosoma cruzi. J Bioenerg Biomembr 26(2):157–165

    Article  CAS  Google Scholar 

  • Chagas, C. (1909). Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem. Mem. Inst. Oswaldo Cruz, 1(2).

  • Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. II. Difference spectra. J Biol Chem 217(1):395–407

    CAS  Google Scholar 

  • Chaudhuri M, Ott RD, Hill GC (2006) Trypanosome alternative oxidase: from molecule to function. Trends Parasitol 22(10):484–491

    Article  CAS  Google Scholar 

  • Coustou V, Besteiro S, Biran M, Diolez P, Bouchaud V, Voisin P et al (2003) ATP generation in the Trypanosoma brucei procyclic form: cytosolic substrate level is essential, but not oxidative phosphorylation. J Biol Chem 278(49):49625–49635

    Article  CAS  Google Scholar 

  • de Meirelles MN, De Souza W (1982) Trypanosoma cruzi: ultrastructural cytochemistry of mitochondrial enzymes. Exp Parasitol 53(3):341–354

    Article  Google Scholar 

  • Denicola-Seoane A, Rubbo H, Prodanov E, Turrens JF (1992) Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes. Mol Biochem Parasitol 54(1):43–50

    Article  CAS  Google Scholar 

  • Dias JC (2007) Globalization, inequity and Chagas disease. Cad Saude Publica 23(Suppl 1):S13–22

    Article  Google Scholar 

  • Docampo R (1993) Calcium homeostasis in Trypanosoma cruzi. Biol Res 26(1–2):189–196

    CAS  Google Scholar 

  • Docampo R, Moreno SN, Vercesi AE (1993) Effect of thapsigargin on calcium homeostasis in Trypanosoma cruzi trypomastigotes and epimastigotes. Mol Biochem Parasitol 59(2):305–313

    Article  CAS  Google Scholar 

  • Ferguson M, Mockett RJ, Shen Y, Orr WC, Sohal RS (2005) Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster. Biochem J 390(Pt 2):501–511

    CAS  Google Scholar 

  • Harington JS (1956) Histamine and histidine in excreta of the blood-sucking bug Rhodnius prolixus. Nature 178(4527):268

    Article  CAS  Google Scholar 

  • Harington JS (1961) Studies of the amino acids of Rhodnius prolixus I. Analysis of the haemolymph. Parasitology 51:309–318

    Article  CAS  Google Scholar 

  • Herrero A, Barja G (1997) ADP-regulation of mitochondrial free radical production is different with complex I-or complex II-linked substrates: implications for the exercise paradox and brain hypermetabolism. J Bioenerg Biomembr 29(3):241–249

    Article  CAS  Google Scholar 

  • Irigoin F, Cibils L, Comini MA, Wilkinson SR, Flohe L, Radi R (2008) Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification. Free Radic Biol Med 45(6):733–742

    Article  CAS  Google Scholar 

  • Japiassu AM, Santiago AP, d’Avila Jda C, Garcia-Souza LF, Galina A, Castro Faria-Neto HC et al (2011) Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5′-triphosphate synthase activity. Crit Care Med 39(5):1056–1063

    Article  CAS  Google Scholar 

  • Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416(1):15–18

    Article  CAS  Google Scholar 

  • Kowaltowski AJ, de Souza-Pinto NC, Castilho RF, Vercesi AE (2009) Mitochondria and reactive oxygen species. Free Radic Biol Med 47(4):333–343

    Article  CAS  Google Scholar 

  • Lamour N, Riviere L, Coustou V, Coombs GH, Barrett MP, Bringaud F (2005) Proline metabolism in procyclic Trypanosoma brucei is down-regulated in the presence of glucose. J Biol Chem 280(12):11902–11910

    Article  CAS  Google Scholar 

  • Lehane MJ (2005) The Biology of Blood-sucking in Insects, 2nd edn. Cambridge University, press, UK

    Book  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25(4):402–408

    Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  Google Scholar 

  • Menna-Barreto RF, Goncalves RL, Costa EM, Silva RS, Pinto AV, Oliveira MF et al (2009) The effects on Trypanosoma cruzi of novel synthetic naphthoquinones are mediated by mitochondrial dysfunction. Free Radic Biol Med 47(5):644–653

    Article  CAS  Google Scholar 

  • Michels PA, Bringaud F, Herman M, Hannaert V (2006) Metabolic functions of glycosomes in trypanosomatids. Biochim Biophys Acta 1763(12):1463–1477

    Article  CAS  Google Scholar 

  • Mielniczki-Pereira AA, Chiavegatto CM, Lopez JA, Colli W, Alves MJ, Gadelha FR (2007) Trypanosoma cruzi strains, Tulahuen 2 and Y, besides the difference in resistance to oxidative stress, display differential glucose-6-phosphate and 6-phosphogluconate dehydrogenases activities. Acta Trop 101(1):54–60

    Article  CAS  Google Scholar 

  • Nicholls DG, Ferguson SJ (2002) Bioenergetics 3, 3rd edn. London, Academic Press, pp 82–83

  • Pan Y, Schroeder EA, Ocampo A, Barrientos A, Shadel GS (2011) Regulation of Yeast Chronological Life Span by TORC1 via Adaptive Mitochondrial ROS Signaling. Cell Metab 13(6):668–678

    Article  CAS  Google Scholar 

  • Piacenza L, Peluffo G, Alvarez MN, Kelly JM, Wilkinson SR, Radi R (2008) Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage-and endogenously-derived peroxynitrite. Biochem J 410(2):359–368

    Article  CAS  Google Scholar 

  • Piacenza L, Zago MP, Peluffo G, Alvarez MN, Basombrio MA, Radi R (2009) Enzymes of the antioxidant network as novel determiners of Trypanosoma cruzi virulence. Int J Parasitol 39(13):1455–1464

    Article  CAS  Google Scholar 

  • Poyton RO, McEwen JE (1996) Crosstalk between nuclear and mitochondrial genomes. Annu Rev Biochem 65:563–607

    Article  CAS  Google Scholar 

  • Rogerson GW, Gutteridge WE (1980) Catabolic metabolism in Trypanosoma cruzi. Int J Parasitol 10(1):131–135

    Article  CAS  Google Scholar 

  • Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386

    CAS  Google Scholar 

  • Silber AM, Tonelli RR, Lopes CG, Cunha-e-Silva N, Torrecilhas AC, Schumacher RI et al (2009) Glucose uptake in the mammalian stages of Trypanosoma cruzi. Mol Biochem Parasitol 168(1):102–108

    Article  CAS  Google Scholar 

  • Silva TM, Peloso EF, Vitor SC, Ribeiro LH, & Gadelha FR (2011). O(2) consumption rates along the growth curve: new insights into Trypanosoma cruzi mitochondrial respiratory chain. J Bioenerg Biomembr. [ahead of print]

  • Tanaka Y, Tanowitz H, Bloom BR (1983) Growth of Trypanosoma cruzi in a cloned macrophage cell line and in a variant defective in oxygen metabolism. Infect Immun 41(3):1322–1331

    CAS  Google Scholar 

  • Tanowitz HB, Weiss LM, Montgomery SP (2011) Chagas disease has now gone global. PLoS Negl Trop Dis 5(4):e1136

    Article  Google Scholar 

  • Tielens AG, Van Hellemond JJ (1998) Differences in energy metabolism between trypanosomatidae. Parasitol Today 14(7):265–272

    Article  CAS  Google Scholar 

  • Tielens AG, van Hellemond JJ (2009) Surprising variety in energy metabolism within Trypanosomatidae. Trends Parasitol 25(10):482–490

    Article  Google Scholar 

  • Vercesi AE, Bernardes CF, Hoffmann ME, Gadelha FR, Docampo R (1991) Digitonin permeabilization does not affect mitochondrial function and allows the determination of the mitochondrial membrane potential of Trypanosoma cruzi in situ. J Biol Chem 266(22):14431–14434

    CAS  Google Scholar 

  • Villani G, Attardi G (2000) In vivo control of respiration by cytochrome c oxidase in human cells. Free Radic Biol Med 29(3–4):202–210

    Article  CAS  Google Scholar 

  • Villani G, Greco M, Papa S, Attardi G (1998) Low reserve of cytochrome c oxidase capacity in vivo in the respiratory chain of a variety of human cell types. J Biol Chem 273(48):31829–31836

    Article  CAS  Google Scholar 

  • Votyakova TV, Reynolds IJ (2004) Detection of hydrogen peroxide with Amplex Red: interference by NADH and reduced glutathione auto-oxidation. Arch Biochem Biophys 431(1):138–144

    Article  CAS  Google Scholar 

  • Zuckerbraun BS, Chin BY, Bilban M, d’Avila JC, Rao J, Billiar TR et al (2007) Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species. FASEB J 21(4):1099–1106

    Article  CAS  Google Scholar 

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Correspondence to Marcus F. Oliveira.

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This work is dedicated to the memory of the honorable Brazilian scientist, teacher and human being Dr. Henrique Leonel Lenzi (1943–2011).

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Gonçalves, R.L.S., Barreto, R.F.S.M., Polycarpo, C.R. et al. A comparative assessment of mitochondrial function in epimastigotes and bloodstream trypomastigotes of Trypanosoma cruzi . J Bioenerg Biomembr 43, 651–661 (2011). https://doi.org/10.1007/s10863-011-9398-8

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  • DOI: https://doi.org/10.1007/s10863-011-9398-8

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