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Translocation of solutes and proteins across the glycosomal membrane of trypanosomes; possibilities and limitations for targeting with trypanocidal drugs

Published online by Cambridge University Press:  23 August 2012

MELISA GUALDRÓN-LÓPEZ ,
ANA BRENNAND ,
LUISANA AVILÁN  and
PAUL A. M. MICHELS
MELISA GUALDRÓN-LÓPEZ
Affiliation:
Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium
ANA BRENNAND
Affiliation:
Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium
LUISANA AVILÁN
Affiliation:
Laboratorio de Fisiología, Facultad de Ciencias, Universidad de los Andes, La Hechicera, 5101 Mérida, Venezuela
PAUL A. M. MICHELS*
Affiliation:
Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium
*
*Corresponding author: Research Unit for Tropical Diseases, de Duve Institute, Université catholique de Louvain, Avenue Hippocrate 74, Postal Box B1.74.01, B-1200 Brussels, Belgium. Tel: +32 (0) 2 7647473. E-mail: [email protected]
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Summary

Glycosomes are specialized peroxisomes found in all kinetoplastid organisms. The organelles are unique in harbouring most enzymes of the glycolytic pathway. Matrix proteins, synthesized in the cytosol, cofactors and metabolites have to be transported across the membrane. Recent research on Trypanosoma brucei has provided insight into how these translocations across the membrane occur, although many details remain to be elucidated. Proteins are imported by a cascade of reactions performed by specialized proteins, called peroxins, in which a cytosolic receptor with bound matrix protein inserts itself in the membrane to deliver its cargo into the organelle and is subsequently retrieved from the glycosome to perform further rounds of import. Bulky solutes, such as cofactors and acyl-CoAs, seem to be translocated by specific transporter molecules, whereas smaller solutes such as glycolytic intermediates probably cross the membrane through pore-forming channels. The presence of such channels is in apparent contradiction with previous results that suggested a low permeability of the glycosomal membrane. We propose 3 possible, not mutually exclusive, solutions for this paradox. Glycosomal glycolytic enzymes have been validated as drug targets against trypanosomatid-borne diseases. We discuss the possible implications of the new data for the design of drugs to be delivered into glycosomes.

Keywords

trypanosomesglycosomeglycosomal membraneABC transporterschannelsmatrix protein importsolute translocationmulti-enzyme complexmetabolite channellingdrug targeting
Type
Review Article
Information
Parasitology , Volume 140 , Issue 1 , January 2013 , pp. 1 - 20
Copyright
Copyright © Cambridge University Press 2012

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References

REFERENCES

Agrimi, G., Russo, A., Scarcia, P. and Palmieri, F. (2012). The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+. The Biochemical Journal 443, 241–247.CrossRefGoogle Scholar
Albert, M. A., Haanstra, J. R., Hannaert, V., Van Roy, J., Opperdoes, F. R., Bakker, B. M. and Michels, P. A. M. (2005). Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei. The Journal of Biological Chemistry 280, 28306–28315.CrossRefGoogle ScholarPubMed
Alsford, S., Eckert, S., Baker, N., Glover, L., Sanchez-Flores, A., Leung, K. F., Turner, D. J., Field, M. C., Berriman, M. and Horn, D. (2012). High-throughput decoding of antitrypanosomal drug efficacy and resistance. Nature, London 482, 232–236.CrossRefGoogle ScholarPubMed
Aman, R. A., Kenyon, G. L. and Wang, C. C. (1985). Cross-linking of the enzymes in the glycosome of Trypanosoma brucei. The Journal of Biological Chemistry 260, 6966–6973.CrossRefGoogle ScholarPubMed
Aman, R. A. and Wang, C. C. (1986). Absence of substrate channeling in the glycosome of Trypanosoma brucei. Molecular and Biochemical Parasitology 19, 1–10.CrossRefGoogle ScholarPubMed
Antonenkov, V. D. and Hiltunen, J. K. (2012). Transfer of metabolites across the peroxisomal membrane. Biochimica et Biophysica Acta 1822, 1374–1386.CrossRefGoogle ScholarPubMed
Antonenkov, V. D., Mindthoff, S., Grunau, S., Erdmann, R. and Hiltunen, J. K. (2009). An involvement of yeast peroxisomal channels in transmembrane transfer of glyoxylate cycle intermediates. The International Journal of Biochemistry & Cell Biology 41, 2546–2554.CrossRefGoogle ScholarPubMed
Antonenkov, V. D., Rokka, A., Sormunen, R. T., Benz, R. and Hiltunen, J. K. (2005). Solute traffic across mammalian peroxisomal membrane − single channel conductance monitoring reveals pore-forming activities in peroxisomes. Cellular and Molecular Life Sciences 62, 2886–2895.CrossRefGoogle ScholarPubMed
Antonenkov, V. D., Sormunen, R. T. and Hiltunen, J. K. (2004). The rat liver peroxisomal membrane forms a permeability barrier for cofactors but not for small metabolites in vitro. Journal of Cell Science 117, 5633–5642.CrossRefGoogle Scholar
Ardelli, B. F., Witt, J. D. and Woo, P. T. (2000). Identification of glycosomes and metabolic end products in pathogenic and nonpathogenic strains of Cryptobia salmositica (Kinetoplastida: Bodonidae). Diseases of Aquatic Organisms 42, 41–51.CrossRefGoogle ScholarPubMed
Aronov, A. M., Suresh, S., Buckner, F. S., Van Voorhis, W. C., Verlinde, C. L., Opperdoes, F. R., Hol, W. G. J. and Gelb, M. H. (1999). Structure-based design of submicromolar, biologically active inhibitors of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase. Proceedings of the National Academy of Sciences of the United States of America 96, 4273–4278.CrossRefGoogle ScholarPubMed
Azéma, L., Lherbet, C., Baudoin, C. and Blonski, C. (2006). Cell permeation of a Trypanosoma brucei aldolase inhibitor: evaluation of different enzyme-labile phosphate protecting groups. Bioorganic & Medicinal Chemistry Letters 16, 3440–3443.CrossRefGoogle ScholarPubMed
Bakker, B. M., Mensonides, F. I., Teusink, B., Van Hoek, P., Michels, P. A. M. and Westerhoff, H. V. (2000). Compartmentation protects trypanosomes from the dangerous design of glycolysis. Proceedings of the National Academy of Sciences, USAmerica 97, 2087–2092.CrossRefGoogle ScholarPubMed
Bakker, B. M., Michels, P. A. M., Opperdoes, F. R. and Westerhoff, H. V. (1997). Glycolysis in bloodstream form Trypanosoma brucei can be understood in terms of the kinetics of the glycolytic enzymes. The Journal of Biological Chemistry 272, 3207–3215.CrossRefGoogle ScholarPubMed
Bakker, B. M., Westerhoff, H. V. and Michels, P. A. M. (1995). Regulation and control of compartmentalized glycolysis in bloodstream form Trypanosoma brucei. Journal of Bioenergetics and Biomembranes 27, 513–525.CrossRefGoogle ScholarPubMed
Beeckmans, S. and Kanarek, L. (1987). Enzyme-enzyme interactions as modulators of the metabolic flux through the citric acid cycle. Biochemical Society Symposium 54, 163–172.Google ScholarPubMed
Brennand, A., Rigden, D. J. and Michels, P. A. M. (2012). Trypanosomes contain two highly different isoforms of peroxin PEX13 involved in glycosome biogenesis. FEBS Letters 586, 1765–1771.CrossRefGoogle ScholarPubMed
Bressi, J. C., Choe, J., Hough, M. T., Buckner, F. S., Van Voorhis, W. C., Verlinde, C. L., Hol, W. G. J. and Gelb, M. H. (2000). Adenosine analogues as inhibitors of Trypanosoma brucei phosphoglycerate kinase: elucidation of a novel binding mode for a 2-amino-N6-substituted adenosine. Journal of Medicinal Chemistry 43, 4135–4150.CrossRefGoogle ScholarPubMed
Bressi, J. C., Verlinde, C. L., Aronov, A. M., Shaw, M. L., Shin, S. S., Nguyen, L. N., Suresh, S., Buckner, F. S., Van Voorhis, W. C., Kuntz, I. D., Hol, W. G. J. and Gelb, M. H. (2001). Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design. Journal of Medicinal Chemistry 44, 2080–2093.CrossRefGoogle ScholarPubMed
Brett, C. L., Donowitz, M. and Rao, R. (2006). Does the proteome encode organellar pH? FEBS Letters 580, 717–719.CrossRefGoogle ScholarPubMed
Brocard, C. and Hartig, A. (2006). Peroxisome targeting signal 1: is it really a simple tripeptide? Biochimica et Biophysica Acta 1763, 1565–1573.CrossRefGoogle ScholarPubMed
Cáceres, A. J., Portillo, R., Acosta, H., Rosales, D., Quiñones, W., Avilan, L., Salazar, L., Dubourdieu, M., Michels, P. A. and Concepción, J. L. (2003). Molecular and biochemical characterization of hexokinase from Trypanosoma cruzi. Molecular and Biochemical Parasitology 126, 251–262.CrossRefGoogle ScholarPubMed
Cáceres, A. J., Michels, P. A. M. and Hannaert, V. (2010). Genetic validation of aldolase and glyceraldehyde-3-phosphate dehydrogenase as drug targets in Trypanosoma brucei. Molecular and Biochemical Parasitology 169, 50–54.CrossRefGoogle ScholarPubMed
Cáceres, A. J., Quiñones, W., Gualdrón, M., Cordeiro, A., Avilán, L., Michels, P. A. and Concepción, J. L. (2007). Molecular and biochemical characterization of novel glucokinases from Trypanosoma cruzi and Leishmania spp. Molecular and Biochemical Parasitology 156, 235–245.CrossRefGoogle ScholarPubMed
Campanella, M. E., Chu, H. and Low, P. S. (2005). Assembly and regulation of a glycolytic enzyme complex on the human erythrocyte membrane. Proceedings of the National Academy of Sciences of the United States of America 102, 2402–2407.CrossRefGoogle ScholarPubMed
Chambers, J. W., Kearns, M. T., Morris, M. T. and Morris, J. C. (2008). Assembly of heterohexameric trypanosome hexokinases reveals that hexokinase 2 is a regulable enzyme. The Journal of Biological Chemistry 283, 14963–14970.CrossRefGoogle ScholarPubMed
Chevalier, N., Bertrand, L., Rider, M. H., Opperdoes, F. R., Rigden, D. J. and Michels, P. A. M. (2005). 6-Phosphofructo-2-kinase and fructose-2,6-bisphosphatase in Trypanosomatidae. Molecular characterization, database searches, modelling studies and evolutionary analysis. The FEBS Journal 272, 3542–3560.CrossRefGoogle ScholarPubMed
Christova, T. Y., Orosz, F. and Ovádi, J. (1996). Interaction between D-glyceraldehyde-3-phosphate dehydrogenase and calmodulin. Biochemical and Biophysical Research Communications 228, 272–277.CrossRefGoogle ScholarPubMed
Clegg, J. S. and Jackson, S. A. (1990). Glucose metabolism and the channeling of glycolytic intermediates in permeabilized L-929 cells. Archives of Biochemistry and Biophysics 278, 452–460.CrossRefGoogle ScholarPubMed
Colasante, C., Alibu, V. P., Kirchberger, S., Tjaden, J., Clayton, C. and Voncken, F. (2006). Characterization and developmentally regulated localization of the mitochondrial carrier protein homologue MCP6 from Trypanosoma brucei. Eukaryotic Cell 5, 1194–1205.CrossRefGoogle ScholarPubMed
Colasante, C., Peña Diaz, P., Clayton, C. and Voncken, F. (2009). Mitochondrial carrier family inventory of Trypanosoma brucei brucei: Identification, expression and subcellular localisation. Molecular and Biochemical Parasitology 167, 104–117.CrossRefGoogle ScholarPubMed
Dax, C., Duffieux, F., Chabot, N., Coincon, M., Sygusch, J., Michels, P. A. M. and Blonski, C. (2006). Selective irreversible inhibition of fructose 1,6-bisphosphate aldolase from Trypanosoma brucei. Journal of Medicinal Chemistry 49, 1499–1502.CrossRefGoogle ScholarPubMed
Denise, H., Giroud, C., Barrett, M. P. and Baltz, T. (1999). Affinity chromatography using trypanocidal arsenical drugs identifies a specific interaction between glycerol-3-phosphate dehydrogenase from Trypanosoma brucei and Cymelarsan. European Journal of Biochemistry 259, 339–346.CrossRefGoogle ScholarPubMed
Dobson, P. D. and Kell, D. B. (2008). Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? Nature Reviews. Drug Discovery 7, 205–220.CrossRefGoogle ScholarPubMed
Dobson, P. D., Lanthaler, K., Oliver, S. G. and Kell, D. B. (2009). Implications of the dominant role of transporters in drug uptake by cells. Current Topics in Medicinal Chemistry 9, 163–181.CrossRefGoogle ScholarPubMed
Dodson, H. C., Lyda, T. A., Chambers, J. W., Morris, M. T., Christensen, K. A. and Morris, J. C. (2011). Quercetin, a fluorescent bioflavanoid, inhibits Trypanosoma brucei hexokinase 1. Experimental Parasitology 127, 423–428.CrossRefGoogle ScholarPubMed
Erdmann, R. and Schliebs, W. (2005). Peroxisomal matrix protein import: the transient pore model. Nature Reviews. Molecular Cell Biology 6, 738–742.CrossRefGoogle ScholarPubMed
Faber, K. N., Van Dijk, R., Keizer-Gunnink, I., Koek, A., Van der Klei, I. J. and Veenhuis, M. (2002). Import of assembled PTS1 proteins into peroxisomes of the yeast Hansenula polymorpha: yes and no! Biochimica et Biophysica Acta 1591, 157–162.CrossRefGoogle ScholarPubMed
Foucher, A. L., McIntosh, A., Douce, G., Wastling, J., Tait, A. and Turner, C. M. (2006). A proteomic analysis of arsenical drug resistance in Trypanosoma brucei. Proteomics 6, 2726–2732.CrossRefGoogle ScholarPubMed
Furuya, T., Kessler, P., Jardim, A., Schnaufer, A., Crudder, C. and Parsons, M. (2002). Glucose is toxic to glycosome-deficient trypanosomes. Proceedings of the National Academy of Sciences of the United States of America 99, 14177–14182.CrossRefGoogle ScholarPubMed
Galland, N., Demeure, F., Hannaert, V., Verplaetse, E., Van Der Smissen, P., Courtoy, P. and Michels, P. A. M. (2007). Characterization of the role of the receptors PEX5 and PEX7 in the import of proteins into glycosomes of Trypanosoma brucei. Biochimica et Biophysica Acta 1773, 521–535.CrossRefGoogle ScholarPubMed
Galland, N. and Michels, P. A. M. (2010). Comparison of the peroxisomal matrix protein import system of different organisms. Exploration of possibilities for developing inhibitors of the import system of trypanosomatids for anti-parasite chemotherapy. European Journal of Cell Biology 89, 621–637.CrossRefGoogle ScholarPubMed
Galland, N., de Walque, S., Voncken, F. G. J., Verlinde, C. L. M. J. and Michels, P. A. M. (2010). An internal sequence targets Trypanosoma brucei triosephosphate isomerase to glycosomes. Molecular and Biochemical Parasitology 171, 45–49.CrossRefGoogle ScholarPubMed
Gatto, G. J. Jr., Geisbrecht, B. V., Gould, S. J. and Berg, J. M. (2000). Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5. Nature Structural & Molecular Biology 7, 1091–1095.Google ScholarPubMed
Ghose, A. K., Herbertz, T., Hudkins, R. L., Dorsey, B. D. and Mallamo, J. P. (2012). Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery. American Chemical Society Chemical Neuroscience 3, 50–68.CrossRefGoogle ScholarPubMed
Girzalsky, W., Platta, H. W. and Erdmann, R. (2009). Protein transport across the peroxisomal membrane. Biological Chemistry 390, 745–751.CrossRefGoogle ScholarPubMed
Grunau, S., Mindthoff, S., Rottensteiner, H., Sormunen, R. T., Hiltunen, J. K., Erdmann, R. and Antonenkov, V. D. (2009). Channel-forming activities of peroxisomal membrane proteins from the yeast Saccharomyces cerevisiae. The FEBS Journal 276, 1698–1708.CrossRefGoogle ScholarPubMed
Gualdrón-López, M., Brennand, A., Hannaert, V., Quiñones, W., Cáceres, A. J., Bringaud, F., Concepción, J. L. and Michels, P. A. M. (2012 a). When, how and why glycolysis became compartmentalised in the Kinetoplastea. A new look at an ancient organelle. International Journal for Parasitology 42, 1–20.CrossRefGoogle Scholar
Gualdrón-López, M., Michels, P. A. M., Quiñones, W., Cáceres, A. J., Avilán, L. and Concepción, J. L. (2012 c). The function of glycosomes in the metabolism of trypanosomatid parasites and the promise of glycosomal proteins as drug targets. In Drug Discovery for Trypanosomatid Diseases; Drug Discovery in Infectious Diseases, Vol. IV. (ed. Jäger, T., Koch, O. and Flohé, L.), Wiley-Blackwell. (in the Press.)Google Scholar
Gualdrón-López, M., Vapola, M. H., Miinalainen, I. J., Hiltunen, J. K., Michels, P. A. M. and Antonenkov, V. D. (2012 b). Channel-forming activities in the glycosomal fraction from the bloodstream form of Trypanosoma brucei. PLoS ONE 7(4): e34530.CrossRefGoogle ScholarPubMed
Haanstra, J. R., Kerkhoven, E. J., Van Tuijl, A., Blits, M., Wurst, M., Van Nuland, R., Albert, M. A., Michels, P. A. M., Bouwman, J., Clayton, C., Westerhoff, H. V. and Bakker, B. M. (2011). A domino effect in drug action: from metabolic assault towards parasite differentiation. Molecular Microbiology 79, 94–108.CrossRefGoogle ScholarPubMed
Haanstra, J. R., Van Tuijl, A., Kessler, P., Reijnders, W., Michels, P. A. M., Westerhoff, H. V., Parsons, M. and Bakker, B. M. (2008). Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes. Proceedings of the National Academy of Sciences of the United States of America 105, 17718–17723.CrossRefGoogle ScholarPubMed
Hammond, D. J., Aman, R. A. and Wang, C. C. (1985). The role of compartmentation and glycerol kinase in the synthesis of ATP within the glycosome of Trypanosoma brucei. The Journal of Biological Chemistry 260, 15646–15654.CrossRefGoogle ScholarPubMed
Hannaert, V. and Michels, P. A. M. (1994). Structure, function, and biogenesis of glycosomes in Kinetoplastida. Journal of Bioenergetics and Biomembranes 26, 205–212.CrossRefGoogle ScholarPubMed
Hart, D. T. and Opperdoes, F. R. (1984). The occurrence of glycosomes (microbodies) in the promastigote stage of four major Leishmania species. Molecular and Biochemical Parasitology 13, 159–172.CrossRefGoogle ScholarPubMed
Häusler, T., Stierhof, Y. D., Wirtz, E. and Clayton, C. (1996). Import of a DHFR hybrid protein into glycosomes in vivo is not inhibited by the folate-analogue aminopterin. The Journal of Cell Biology 132, 311–324.CrossRefGoogle Scholar
Helfert, S., Estévez, A. M., Bakker, B., Michels, P. and Clayton, C. (2001). Roles of triosephosphate isomerase and aerobic metabolism in Trypanosoma brucei. The Biochemical Journal 357, 117–125.CrossRefGoogle ScholarPubMed
Hudock, M. P., Sanz-Rodríguez, C. E., Song, Y., Chan, J. M., Zhang, Y., Odeh, S., Kosztowski, T., Leon-Rossell, A., Concepción, J. L., Yardley, V., Croft, S. L., Urbina, J. A. and Oldfield, E. (2006). Inhibition of Trypanosoma cruzi hexokinase by bisphosphonates. Journal of Medicinal Chemistry 49, 215–223.CrossRefGoogle ScholarPubMed
Hyde, C. C., Ahmed, S. A., Padlan, E. A., Miles, E. W. and Davies, D. R. (1988). Three-dimensional structure of the tryptophan synthase α 2β2 multienzyme complex from Salmonella typhimurium. The Journal of Biological Chemistry 263, 17857–17871.CrossRefGoogle Scholar
Igoillo-Esteve, M., Mazet, M., Deumer, G., Wallemacq, P. and Michels, P. A. M. (2011). Glycosomal ABC transporters of Trypanosoma brucei: characterisation of their expression, topology and substrate specificity. International Journal for Parasitology 41, 429–438.CrossRefGoogle ScholarPubMed
Islam, M. M., Nautiyal, M., Wynn, R. M., Mobley, J. A., Chuang, D. T. and Hutson, S. M. (2010). Branched-chain amino acid metabolon: interaction of glutamate dehydrogenase with the mitochondrial branched-chain aminotransferase (BCATm). The Journal of Biological Chemistry 285, 265–276.CrossRefGoogle ScholarPubMed
Jørgensen, K., Rasmussen, A. V., Morant, M., Nielsen, A. H., Bjarnholt, N., Zagrobelny, M., Bak, S. and Møller, B. L. (2005). Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Current Opinion in Plant Biology 8, 280–291.CrossRefGoogle ScholarPubMed
Kell, D. B., Dobson, P. D. and Oliver, S. G. (2011). Pharmaceutical drug transport: the issues and the implications that it is essentially carrier-mediated only. Drug Discovery Today 16, 704–714.CrossRefGoogle ScholarPubMed
Lanthaler, K., Bilsland, E., Dobson, P. D., Moss, H. J., Pir, P., Kell, D. B. and Oliver, S. G. (2011). Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast. BMC Biology 9, 70.CrossRefGoogle Scholar
Lazarow, P. B. (2006). The import receptor Pex7p and the PTS2 targeting sequence. Biochimica et Biophysica Acta 1763, 1599–1604.CrossRefGoogle ScholarPubMed
Léon, S., Goodman, J. M. and Subramani, S. (2006). Uniqueness of the mechanism of protein import into the peroxisome matrix: transport of folded, co-factor-bound and oligomeric proteins by shuttling receptors. Biochimica et Biophysica Acta 1763, 1552–1564.CrossRefGoogle ScholarPubMed
Lipinski, C. A., Lombardo, F., Dominy, B. W. and Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 46, 3–26.CrossRefGoogle ScholarPubMed
Maugeri, D. A., Cannata, J. J. and Cazzulo, J. J. (2011). Glucose metabolism in Trypanosoma cruzi. Essays in Biochemistry 51, 15–30.Google ScholarPubMed
McConville, M. J. and Naderer, T. (2011). Metabolic pathways required for the intracellular survival of Leishmania. Annual Review of Microbiology 65, 543–561.CrossRefGoogle ScholarPubMed
McNew, J. A. and Goodman, J. M. (1994). An oligomeric protein is imported into peroxisomes in vivo. The Journal of Cell Biology 127, 1245–1257.CrossRefGoogle ScholarPubMed
Meinecke, M., Cizmowski, C., Schliebs, W., Krüger, V., Beck, S., Wagner, R. and Erdmann, R. (2010). The peroxisomal importomer constitutes a large and highly dynamic pore. Nature Cell Biology 12, 273–277.CrossRefGoogle ScholarPubMed
Meyer, F. M., Gerwig, J., Hammer, E., Herzberg, C., Commichau, F. M., Völker, U. and Stülke, J. (2011). Physical interactions between tricarboxylic acid cycle enzymes in Bacillus subtilis: evidence for a metabolon. Metabolic Engineering 13, 18–27.CrossRefGoogle ScholarPubMed
Michels, P. A. M., Bringaud, F., Herman, M. and Hannaert, V. (2006). Metabolic functions of glycosomes in trypanosomatids. Biochimica et Biophysica Acta 1763, 1463–1477.CrossRefGoogle ScholarPubMed
Miles, E. W., Rhee, S. and Davies, D. R. (1999). The molecular basis of substrate channeling. The Journal of Biological Chemistry 274, 12193–12196.CrossRefGoogle ScholarPubMed
Misset, O., Bos, O. J. M. and Opperdoes, F. R. (1986). Glycolytic enzymes of Trypanosoma brucei. Simultaneous purification, intraglycosomal concentrations and physical properties. European Journal of Biochemistry 157, 441–453.CrossRefGoogle ScholarPubMed
Misset, O. and Opperdoes, F. R. (1984). Simultaneous purification of hexokinase, class-I fructose-bisphosphate aldolase, triosephosphate isomerase and phosphoglycerate kinase from Trypanosoma brucei. European Journal of Biochemistry 144, 475–483.CrossRefGoogle ScholarPubMed
Morita, M. and Imanaka, T. (2012). Peroxisomal ABC transporters: Structure, function and role in disease. Biochimica et Biophysica Acta 1822, 1387–1396.CrossRefGoogle ScholarPubMed
Moyersoen, J., Choe, J., Fan, E., Hol, W. G. J. and Michels, P. A. M. (2004). Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target. FEMS Microbiology Reviews 28, 603–643.CrossRefGoogle ScholarPubMed
Naderer, T. and McConville, M. J. (2011). Intracellular growth and pathogenesis of Leishmania parasites. Essays in Biochemistry 51, 81–95.Google ScholarPubMed
Nair, D. M., Purdue, P. E. and Lazarow, P. B. (2004). Pex7p translocates in and out of peroxisomes in Saccharomyces cerevisiae. The Journal of Cell Biology 167, 599–604.CrossRefGoogle ScholarPubMed
Nowicki, M. W., Tulloch, L. B., Worrall, L., McNae, I. W., Hannaert, V., Michels, P. A. M., Fothergill-Gilmore, L. A., Walkinshaw, M. D. and Turner, N. J. (2008). Design, synthesis and trypanocidal activity of lead compounds based on inhibitors of parasite glycolysis. Bioorganic & Medicinal Chemistry 16, 5050–5061.CrossRefGoogle ScholarPubMed
Opperdoes, F. R. (1985). Biochemical peculiarities of trypanosomes, African and South American. British Medical Bulletin 41, 130–136.CrossRefGoogle ScholarPubMed
Opperdoes, F. R., Baudhuin, P., Coppens, I., De Roe, C., Edwards, S. W., Weijers, P. J. and Misset, O. (1984). Purification, morphometric analysis, and characterization of the glycosomes (microbodies) of the protozoan hemoflagellate Trypanosoma brucei. The Journal of Cell Biology 98, 1178–1184.CrossRefGoogle ScholarPubMed
Opperdoes, F. R. and Borst, P. (1977). Localization of nine glycolytic enzymes in a microbody-like organelle in Trypanosoma brucei: the glycosome. FEBS Letters 80, 360–364.CrossRefGoogle Scholar
Opperdoes, F. R. and Michels, P. A. M. (2001) Enzymes of carbohydrate metabolism as potential drug targets. International Journal for Parasitology 31, 482–490.CrossRefGoogle ScholarPubMed
Opperdoes, F. R., Nohynkova, E., Van Schaftingen, E., Lambeir, A. M., Veenhuis, M. and Van Roy, J. (1988). Demonstration of glycosomes (microbodies) in the Bodonid flagellate Trypanoplasma borelli (Protozoa, Kinetoplastida). Molecular and Biochemical Parasitology 30, 155–163.CrossRefGoogle ScholarPubMed
Ovádi, J. (1988). Old pathway–new concept: control of glycolysis by metabolite-modulated dynamic enzyme associations. Trends in Biochemical Sciences 13, 486–490.CrossRefGoogle ScholarPubMed
Reumann, S. (2000). The structural properties of plant peroxisomes and their metabolic significance. Biological Chemistry 381, 639–648.CrossRefGoogle ScholarPubMed
Ricard, J., Gontero, B., Avilán, L. and Lebreton, S. (1998). Enzymes and the supramolecular organization of the living cell. Information transfer within supramolecular edifices and imprinting effects. Cellular and Molecular Life Sciences 54, 1231–1248.CrossRefGoogle Scholar
Rokka, A., Antonenkov, V. D., Soininen, R., Immonen, H. L., Pirilä, P. L., Bergmann, U., Sormunen, R. T., Weckström, M., Benz, R. and Hiltunen, J. K. (2009). Pxmp2 is a channel-forming protein in mammalian peroxisomal membrane. PLoS ONE 4(4), e5090.CrossRefGoogle ScholarPubMed
Rucktäschel, R., Girzalsky, W. and Erdmann, R. (2011). Protein import machineries of peroxisomes. Biochimica et Biophysica Acta 1808, 892–900.CrossRefGoogle ScholarPubMed
Sampathkumar, P., Roach, C., Michels, P. A. M. and Hol, W. G. J. (2008). Structural insights into the recognition of peroxisomal targeting signal 1 by Trypanosoma brucei peroxin 5. Journal of Molecular Biology 381, 867–880.CrossRefGoogle ScholarPubMed
Sánchez-Moreno, M., Lasztity, D., Coppens, I. and Opperdoes, F. R. (1992). Characterization of carbohydrate metabolism and demonstration of glycosomes in a Phytomonas sp. isolated from Euphorbia characias. Molecular and Biochemical Parasitology 54, 185–199.CrossRefGoogle Scholar
Sanz-Rodríguez, C. E., Concepción, J. L., Pekerar, S., Oldfield, E. and Urbina, J. A. (2007). Bisphosphonates as inhibitors of Trypanosoma cruzi hexokinase: kinetic and metabolic studies. Journal of Biological Chemistry 282, 12377–12387.CrossRefGoogle ScholarPubMed
Schliebs, W., Girzalsky, W. and Erdmann, R. (2010). Peroxisomal protein import and ERAD: variations on a common theme. Nature Reviews. Molecular Cell Biology 11, 885–890.CrossRefGoogle ScholarPubMed
Schliebs, W. and Kunau, W. H. (2006). PTS2 co-receptors: diverse proteins with common features. Biochimica et Biophysica Acta 1763, 1605–1612.CrossRefGoogle ScholarPubMed
Schumann-Burkard, G., Jutzi, P. and Roditi, I. (2011). Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters. Molecular and Biochemical Parasitology 175, 91–94.CrossRefGoogle ScholarPubMed
Sharlow, E. R., Lyda, T. A., Dodson, H. C., Mustata, G., Morris, M. T., Leimgruber, S. S., Lee, K. H., Kashiwada, Y., Close, D., Lazo, J. S. and Morris, J. C. (2010). A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity. PLoS Neglected Tropical Diseases 4, e659.CrossRefGoogle ScholarPubMed
Srere, P. A. (1987). Complexes of sequential metabolic enzymes. Annual Review of Biochemistry 156, 89–124.CrossRefGoogle Scholar
Stanley, W. A. and Wilmanns, M. (2006). Dynamic architecture of the peroxisomal import receptor Pex5p. Biochimica et Biophysica Acta 1763, 1592–1598.CrossRefGoogle ScholarPubMed
Sullivan, D. T., MacIntyre, R., Fuda, N., Fiori, J., Barrilla, J. and Ramizel, L. (2003). Analysis of glycolytic enzyme co-localization in Drosophila flight muscle. The Journal of Experimental Biology 206, 2031–2038.CrossRefGoogle ScholarPubMed
Taylor, M. B., Berghausen, H., Heyworth, P., Messenger, N., Rees, L. J. and Gutteridge, W. E. (1980). Subcellular localization of some glycolytic enzymes in parasitic flagellated protozoa. The International Journal of Biochemistry 11, 117–120.CrossRefGoogle ScholarPubMed
Theodoulou, F. L., Holdsworth, M. and Baker, A. (2006). Peroxisomal ABC transporters. FEBS Letters 580, 1139–1155.CrossRefGoogle ScholarPubMed
Titorenko, V. I., Nicaud, J. M., Wang, H., Chan, H. and Rachubinski, R. A. (2002). Acyl-CoA oxidase is imported as a heteropentameric, cofactor-containing complex into peroxisomes of Yarrowia lipolytica. The Journal of Cell Biology 156, 481–494.CrossRefGoogle ScholarPubMed
Van der Klei, I. J. and Veenhuis, M. (2006). PTS1-independent sorting of peroxisomal matrix proteins by Pex5p. Biochimica et Biophysica Acta 1763, 1794–1800.CrossRefGoogle ScholarPubMed
Van Roermund, C. W., Elgersma, Y., Singh, N., Wanders, R. J. A. and Tabak, H. F. (1995). The membrane of peroxisomes in Saccharomyces cerevisiae is impermeable to NAD(H) and acetyl-CoA under in vivo conditions. EMBO Journal 14, 3480–3486.CrossRefGoogle ScholarPubMed
Van Schaftingen, E., Opperdoes, F. R. and Hers, H. G. (1985). Stimulation of Trypanosoma brucei pyruvate kinase by fructose 2,6-bisphosphate. European Journal of Biochemistry 153, 403–406.CrossRefGoogle ScholarPubMed
Van Veldhoven, P. P., Just, W. W. and Mannaerts, G. P. (1987). Permeability of the peroxisomal membrane to cofactors of β-oxidation. Evidence for the presence of a pore-forming protein. The Journal of Biological Chemistry 262, 4310–4318.CrossRefGoogle ScholarPubMed
Vélot, C. and Srere, P. A. (2000). Reversible transdominant inhibition of a metabolic pathway. In vivo evidence of interaction between two sequential tricarboxylic acid cycle enzymes in yeast. The Journal of Biological Chemistry 275, 12926–12933.CrossRefGoogle ScholarPubMed
Verlinde, C. L. M. J., Hannaert, V., Blonski, C., Willson, M., Périé, J. J., Fothergill-Gilmore, L. A., Opperdoes, F. R., Gelb, M. H., Hol, W. G. J. and Michels, P. A. M. (2001). Glycolysis as a target for the design of new anti-trypanosome drugs. Drug Resistance Updates 4, 50–65.CrossRefGoogle ScholarPubMed
Verplaetse, E., Rigden, D. J. and Michels, P. A. M. (2009). Identification, characterisation and essentiality of the unusual peroxin 13 from Trypanosoma brucei. Biochimica et Biophysica Acta 1793, 516–527.CrossRefGoogle ScholarPubMed
Vértessy, B. G., Kovács, J. and Ovádi, J. (1997). Specific characteristics of phosphofructokinase-microtubule interaction. FEBS Letters 379, 191–195.CrossRefGoogle Scholar
Visser, N., Opperdoes, F. R. and Borst, P. (1981). Subcellular compartmentation of glycolytic intermediates in Trypanosoma brucei. European Journal of Biochemistry 118, 521–526.CrossRefGoogle ScholarPubMed
Visser, W. F., Van Roermund, C. W., IJlst, L., Waterham, H. R. and Wanders, R. J. A. (2007). Metabolite transport across the peroxisomal membrane. The Biochemical Journal 401, 365–375.CrossRefGoogle ScholarPubMed
Wager, T. T., Villalobos, A., Verhoest, P. R., Hou, X. and Shaffer, C. L. (2011). Strategies to optimize the brain availability of central nervous system drug candidates. Expert Opinion on Drug Discovery 6, 371–381.CrossRefGoogle ScholarPubMed
Wanders, R. J. A. and Tager, J. M. (1998). Lipid metabolism in peroxisomes in relation to human disease. Molecular Aspects of Medicine 19, 69–154.CrossRefGoogle ScholarPubMed
Williams, C. P. and Stanley, W. A. (2010). Peroxin 5: a cycling receptor for protein translocation into peroxisomes. The International Journal of Biochemistry & Cell Biology 42, 1771–1774.CrossRefGoogle ScholarPubMed
Williamson, M. P. and Sutcliffe, M. J. (2010). Protein-protein interactions. Biochemical Society Transactions 38, 875–878.CrossRefGoogle ScholarPubMed
Willson, M., Callens, M., Kuntz, D. A., Périé, J. and Opperdoes, F. R. (1993). Synthesis and activity of inhibitors highly specific for the glycolytic enzymes from Trypanosoma brucei. Molecular and Biochemical Parasitology 59, 201–210.CrossRefGoogle ScholarPubMed
Yernaux, C., Fransen, M., Brees, C., Lorenzen, S. and Michels, P. A. M. (2006). Trypanosoma brucei glycosomal ABC transporters: identification and membrane targeting. Molecular Membrane Biology 23, 157–172.CrossRefGoogle ScholarPubMed