Hostname: page-component-5b777bbd6c-rbv74 Total loading time: 0 Render date: 2025-06-25T11:08:45.399Z Has data issue: false hasContentIssue false
  • English
  • Français

Mitochondria of mammalian Plasmodium spp.

Published online by Cambridge University Press:  06 April 2009

M. Fry  and
J. E. Beesley
M. Fry
Affiliation:
Biochemical Sciences, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK
J. E. Beesley
Affiliation:
Pharmacology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK
Get access Rights & Permissions [Opens in a new window]

Summary

Highly purified mitochondrial fractions have been isolated from the intraerythrocytic stages of two mammalian Plasmodium spp., Plasmodium yoelii of rodents and Plasmodium falciparum of man. Mitochondria of the former parasite are cristate whereas those of the latter are essentially acristate. Isolated mitochondria from both parasite species were heterogeneous with respect to size, shape, density of matrix staining and extent of internal structure. Respiratory assay, by reduction of exogenous cytochrome c, showed NADH, α-glycerophosphate and succinate to be the substrates with the greatest potential for metabolism. Additionally, proline, dihydroorotate and glutamate (P. falciparum only) were oxidized at low rates. A number of NAD+-linked substrates were not utilized. The NADH-dependent reduction of cytochrome c was insensitive to rotenone and antimycin A. Fumarate inhibited the NADH-dependent reduction of cytochrome c and stimulated the oxidation of NADH, suggestive of an NADH–fumarate reductase pathway. Oxidation of either α-glycerophosphate or succinate was fully inhibited by standard mitochondrial electron transport inhibitors, including a number of Complex III inhibitors, although the concentrations required of such inhibitors (notably myxothiazol) were relatively high compared to mammalian mitochondria. Dithionite-reduced minus oxidized difference spectra indicated the presence of cytochromes aa3, b, c and c1 in mitochondria of both parasite species, but at a higher cytochrome to protein ratio in P. yoelii. Freshly isolated mitochondria from either species exhibited only low respiratory control ratios with α-glycerophosphate or succinate as substrates. The apparent absence of a respiratory chain ‘Site I’ in such mitochondria may mean that NADH–fumarate reductase serves to reoxidize mitochondrial NADH.

Keywords

mitochondriamalariaPlasmodium yoeliiPlasmodium falciparum
Type
Research Article
Information
Parasitology , Volume 102 , Issue 1 , February 1991 , pp. 17 - 26
Copyright
Copyright © Cambridge University Press 1991

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Agureev, A. P., Altukhov, N. D., Mokhova, E. N. & Savelev, I. A. (1981). Activation of the external pathway of oxidation of NADH in the mitochondria with decreasing pH. Biokhimiya 46, 1945–56.Google Scholar
Bernardi, P. & Azzone, G. F. (1981). Cytochrome c as an electron shuttle between the outer and inner mitochondrial membranes. Journal of Biological Chemistry 256, 7187–92.CrossRefGoogle ScholarPubMed
Bowyer, J. R. & Trumpower, B. L. (1980). Inhibition of the oxidant-induced reduction of cytochrome b by a synthetic analogue of ubiquinone. FEBS Letters 115, 171–4.CrossRefGoogle ScholarPubMed
Ciaccio, E. I., Boxer, G. E., Devlin, T. M. & Ford, R. T. (1967). Screening data from selected in vitro enzymatic systems. II. Compounds specifically selected for the dehydrogenase inhibitor screens. Cancer Research 27, 1070–104.Google Scholar
Cook, N. D. & Cammack, R. (1984). Purification and characterisation of the rotenone-insensitive NADH–dehydrogenase of mitochondria from Arum maculatum. European Journal of Biochemistry 141, 573–7.CrossRefGoogle ScholarPubMed
Dawson, A. G. (1979). Oxidation of cytosolic NADH formed during aerobic metabolism in mammalian cells. Trends in Biochemical Science 4, 171–6.CrossRefGoogle Scholar
Dawson, A. G. & Cooney, G. J. (1978). Reconstitution of the α-glycerolphosphate shuttle using rat kidney mitochondria. FEBS Letters 91, 169–72.CrossRefGoogle Scholar
Divo, A. A., Geary, T. G., Jensen, J. B. & Ginsburg, H. (1985). The mitochondria of Plasmodium falciparum visualized by rhodamine 123 fluorescence. Journal of Protozoology 32, 442–6.CrossRefGoogle ScholarPubMed
Ernster, L., Bharaj, B. S. & Nordenbrand, K. (1981). Origin of phosphorylation coupled to the oxidation of extramitochondrial NADH. FEBS Letters 132, 6–9.CrossRefGoogle Scholar
Fry, M. (1989). Diferric transferrin reductase in Plasmodium falciparum-infected erythrocytes. Biochemical and Biophysical Research Communications 158, 469–73.CrossRefGoogle ScholarPubMed
Geary, T. G. & Jensen, J. B. (1983). Effects of antibiotics on Plasmodium falciparum in vitro. American Journal of Tropical Medicine and Hygiene 32, 221–5.CrossRefGoogle ScholarPubMed
Ginsburg, H., Divo, A. A., Geary, T. G., Borland, M. T. & Jensen, J. B. (1986). Effects of mitochondrial inhibitors on intraerythrocytic Plasmodium falciparum in in vitro cultures. Journal of Protozoology 33, 121–5.CrossRefGoogle ScholarPubMed
Gutteridge, W. E. & Rogerson, G. W. (1979). Biochemical aspects of the biology of Trypanosoma cruzi. In Biology of the Kinetoplastida Vol. 2 (ed. Lumsden, W. H. R. & Evans, D. A.), pp. 619–52. London: Academic Press.Google Scholar
Izumo, A., Tanabe, K. & Kato, M. (1988). The plasma membrane and mitochondrial membrane potentials of Plasmodium yoelii. Comparative Biochemistry and Physiology 91B, 735–9.Google ScholarPubMed
Kopaczyk, K. C. (1967). Preparation and properties of the heart mitochondrial electron transporting particles (inner membrane). In Methods in Enzymology, Vol. 10 (ed. Estabrook, W. R. & Pullman, M. E.), p. 256. New York and London: Academic Press.Google Scholar
Nelson, B. D., Walter, P. & Ernster, L. (1977). Funiculosin: an antibiotic with antimycin-like inhibitory properties. Biochimica et Biophysica Acta. 460, 157–62.Google Scholar
Pedersen, P. L., Greenwalt, J. W., Reynafarje, B., Hullihen, J., Decker, G. L., Soper, J. W. & Bustamente, E. (1978). Preparation and characterisation of mitochondria and sub-mitochondrial particles of rat liver and liver derived tissues. Methods in Cell Biology 20, 411–81.CrossRefGoogle Scholar
Scheibel, L. W. & Miller, J. (1969). Glycolytic and cytochrome oxidase activity in plasmodia. Military Medicine 134, 1074–80.CrossRefGoogle ScholarPubMed
Sherman, I. W. (1979). Biochemistry of Plasmodium (malarial parasites). Microbiological Reviews 43, 453–95.Google Scholar
Slomianny, C. & Prensier, G. (1986). Application of the serial sectioning and tridimensional reconstruction techniques to the morphological study of the Plasmodium falciparum mitochondrion. Journal of Parasitology 72, 595–8.Google Scholar
Thierbach, G. & Reichenbach, H. (1981). Myxothiazol, a new inhibitor of the cytochrome b-c1 segment of the respiratory chain. Biochimica et Biophysica Acta 638, 282–9.CrossRefGoogle ScholarPubMed
Turrens, J. F. (1989). The role of succinate in the respiratory chain of Trypanosoma brucei procyclic trypomastigotes. The Biochemical Journal 259, 363–8.Google Scholar
Vargas, A. M. (1982). Rapid preparation of metabolically active mitochondria from control and hormone-treated rat liver cells. Journal of Biochemical and Biophysical Methods 7, 1–6.Google Scholar
Walliker, D., Sanderson, A., Yoeli, M. & Hargreaves, B. J. (1976) A genetic investigation of virulence in a rodent malaria parasite. Parasitology 72, 183–94.CrossRefGoogle Scholar
Williams, S. G. & Richards, W. H. G. (1973). Malaria studies in vitro – 1. Techniques for the preparation and culture of leucocyte-free blood dilution cultures of Plasmodia. Annals of Tropical Medicine and Parasitology 67, 169–78.CrossRefGoogle Scholar