Autophagy in trypanosomatids

Cells

Volumn 1, Issue 3, 2012, Pages 346-371

  Brennand, Ana ^a   Rico, Eva ^b,c   Michels, Paul A M ^a  

^a DE DUVE INSTITUTE   (Belgium)

^b UNIVERSITY OF ALCALÁ   (Spain)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Autophagy; Drug action; Drug discovery; Glycosomes; Leishmania; Life cycle differentiation; Parasites; Pexophagy; Trypanosoma; Trypanosomatidae

Indexed keywords

ANTITRYPANOSOMAL AGENT; EDELFOSINE; KETOCONAZOLE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEASOME; RAPAMYCIN; TOXIC SUBSTANCE;

AFRICAN TRYPANOSOMIASIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CHAGAS DISEASE; EPIMASTIGOTE; EXCAVATA; EXPERIMENTAL STUDY; FUNGUS; GLYCOLYSIS; GLYCOSOME; HUMAN; INSECT; KINETOPLASTIDA; LEISHMANIA; LEISHMANIASIS; LIFE CYCLE; MACROAUTOPHAGY; MAMMAL; NONHUMAN; PEXOPHAGY; PICHIA PASTORIS; PROTEIN DEGRADATION; PROTIST; SACCHAROMYCES CEREVISIAE; SURVIVAL; TRYPANOSOMA BRUCEI; TRYPANOSOMA CRUZI; TRYPOMASTIGOTE; VIRULENCE;

EID: 84903073708     PISSN: None     EISSN: 20734409     Source Type: Journal    
DOI: 10.3390/cells1030346     Document Type: Article

References (116)

1. Moreira, D.; Lopez-Garcia, P.; Vickerman, K. An updated view of kinetoplastid phylogeny using environmental sequences and a closer outgroup: Proposal for a new classification of the class Kinetoplastea. Int. J. Syst. Evol. Microbiol. 2004, 54, 1861-1875.
2. de Souza, W.; Attias, M.; Rodrigues, J.C. Particularities of mitochondrial structure in parasitic protists (Apicomplexa and Kinetoplastida). Int. J. Biochem. Cell Biol. 2009, 41, 2069-2080.
3. Dollet, M.; Sturm, N.R.; Campbell, D.A. The internal transcribed spacer of ribosomal RNA genes in plant trypanosomes (Phytomonas spp.) resolves 10 groups. Infect. Genet. Evol. 2012, 12, 299-308.
4. Podlipaev, S.A. Insect trypanosomatids: The need to know more. Memorias do Instituto Oswaldo Cruz 2000, 95, 517-522.
5. Simpson, A.G.; Stevens, J.R.; Lukes, J. The evolution and diversity of kinetoplastid flagellates. Trends Parasitol. 2006, 22, 168-174.
6. Vickerman, K. The evolutionary expansion of the trypanosomatid flagellates. Int. J. Parasitol. 1994, 24, 1317-1331.
7. Zeledon, R.A. Hemoflagellates: Cutaneous and mucocutaneous leishmaniasis. In Barron's Medical Microbiology; University of Texas Medical Branch: Galveston, TX, USA, 1996.
8. Gualdron-Lopez, M.; Brennand, A.; Hannaert, V.; Quinones, W.; Caceres, A.J.; Bringaud, F.; Concepcion, J.L.; Michels, P.A. When, how and why glycolysis became compartmentalised in the Kinetoplastea. A new look at an ancient organelle. Int. J. Parasitol. 2012, 42, 1-20.
9. Michels, P.A.; Bringaud, F.; Herman, M.; Hannaert, V. Metabolic functions of glycosomes in trypanosomatids. Biochim. Biophys. Acta 2006, 1763, 1463-1477.
10. Furuya, T.; Kessler, P.; Jardim, A.; Schnaufer, A.; Crudder, C.; Parsons, M. Glucose is toxic to glycosome-deficient trypanosomes. Proc. Natl. Acad. Sci. USA 2002, 99, 14177-14182.
11. Haanstra, J.R.; van Tuijl, A.; Kessler, P.; Reijnders, W.; Michels, P.A.; Westerhoff, H.V.; Parsons, M.; Bakker, B.M. Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes. Proc. Natl. Acad. Sci. USA 2008, 105, 17718-17723.
12. Teixeira, M.M.; Borghesan, T.C.; Ferreira, R.C.; Santos, M.A.; Takata, C.S.; Campaner, M.; Nunes, V.L.; Milder, R.V.; de Souza, W.; Camargo, E.P. Phylogenetic validation of the genera Angomonas and Strigomonas of trypanosomatids harboring bacterial endosymbionts with the description of new species of trypanosomatids and of proteobacterial symbionts. Protist 2011, 162, 503-524.
13. Rassi, A., Jr.; Rassi, A.; Marin-Neto, J.A. Chagas disease. Lancet 2010, 375, 1388-1402.
14. Barrett, M.P.; Vincent, I.M.; Burchmore, R.J.; Kazibwe, A.J.; Matovu, E. Drug resistance in human African trypanosomiasis. Future Microbiol. 2011, 6, 1037-1047.
15. Kennedy, P.G. The continuing problem of human African trypanosomiasis (sleeping sickness). Ann. Neurol. 2008, 64, 116-126.
16. Desjeux, P. Leishmaniasis: Current situation and new perspectives. Comp. Immunol. Microbiol. Infect. Dis. 2004, 27, 305-318.
17. Piscopo, T.V.; Mallia Azzopardi, C. Leishmaniasis. Postgrad. Med. 2007, 83, 649-657.
18. David, C.V.; Craft, N. Cutaneous and mucocutaneous leishmaniasis. Dermatol. Ther. 2009, 22, 491-502.
19. Moore, E.M.; Lockwood, D.N. Treatment of visceral leishmaniasis. J. Global Infect. Dis. 2010, 2, 151-158.
20. Castillo, E.; Dea-Ayuela, M.A.; Bolas-Fernandez, F.; Rangel, M.; Gonzalez-Rosende, M.E. The kinetoplastid chemotherapy revisited: Current drugs, recent advances and future perspectives. Curr. Med. Chem. 2010, 17, 4027-4051.
21. Simarro, P.P.; Franco, J.; Diarra, A.; Postigo, J.A.; Jannin, J. Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. Parasitology 2012, 139, 842-846.
22. Hoare, C.A. Rationalization of the terminology for the developmental stages of trypanosomatid flagellates. Meditsinskaia parazitologiia i parazitarnye bolezni 1971, 40, 307-309.
23. Fenn, K.; Matthews, K.R. The cell biology of Trypanosoma brucei differentiation. Curr. Opin. Microbiol. 2007, 10, 539-546.
24. de Souza, W.; de Carvalho, T.M.; Barrias, E.S. Review on Trypanosoma cruzi: Host cell interaction. Int. J. Cell Biol. 2010, 2010, pii: 295394.
25. Bates, P.A. Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. Int. J. Parasitol. 2007, 37, 1097-1106.
26. de Duve, C. The lysosome turns fifty. Med. Sci. (Paris) 2005, 21, 12-15.
27. Armstrong, J. Yeast vacuoles: More than a model lysosome. Trends Cell Biol. 2010, 20, 580-585.
28. Klionsky, D.J.; Cregg, J.M.; Dunn, W.A., Jr.; Emr, S.D.; Sakai, Y.; Sandoval, I.V.; Sibirny, A.; Subramani, S.; Thumm, M.; Veenhuis, M.; et al. A unified nomenclature for yeast autophagy-related genes. Dev. Cell 2003, 5, 539-545.
29. Nakatogawa, H.; Suzuki, K.; Kamada, Y.; Ohsumi, Y. Dynamics and diversity in autophagy mechanisms: Lessons from yeast. Nat. Rev. Mol. Cell Bio. 2009, 10, 458-467.
30. Meijer, W.H.; van der Klei, I.J.; Veenhuis, M.; Kiel, J.A. ATG genes involved in non-selective autophagy are conserved from yeast to man, but the selective Cvt and pexophagy pathways also require organism-specific genes. Autophagy 2007, 3, 106-116.
31. Yang, Z.; Klionsky, D.J. An overview of the molecular mechanism of autophagy. Curr. Top. Microbiol. Immunol. 2009, 335, 1-32.
32. Yorimitsu, T.; Klionsky, D.J. Autophagy: Molecular machinery for self-eating. Cell Death Differ. 2005, 12, 1542-1552.
33. Lynch-Day, M.A.; Klionsky, D.J. The Cvt pathway as a model for selective autophagy. FEBS Lett. 2010, 584, 1359-1366.
34. Dunn, W.A., Jr.; Cregg, J.M.; Kiel, J.A.; van der Klei, I.J.; Oku, M.; Sakai, Y.; Sibirny, A.A.; Stasyk, O.V.; Veenhuis, M. Pexophagy: The selective autophagy of peroxisomes. Autophagy 2005, 1, 75-83.
35. Youle, R.J.; Narendra, D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Bio. 2011, 12, 9-14.
36. Roberts, P.; Moshitch-Moshkovitz, S.; Kvam, E.; O'Toole, E.; Winey, M.; Goldfarb, D.S. Piecemeal microautophagy of nucleus in Saccharomyces cerevisiae. Mol. Biol. Cell 2003, 14, 129-141.
37. He, C.; Klionsky, D.J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 2009, 43, 67-93.
38. Kroemer, G.; Levine, B. Autophagic cell death: The story of a misnomer. Nat. Rev. Mol. Cell Bio. 2008, 9, 1004-1010.
39. Mehrpour, M.; Esclatine, A.; Beau, I.; Codogno, P. Overview of macroautophagy regulation in mammalian cells. Cell Res. 2010, 20, 748-762.
40. Shen, S.; Kepp, O.; Kroemer, G. The end of autophagic cell death? Autophagy 2012, 8, 4544-4556.
41. Chen, Z.J.; Sun, L.J. Nonproteolytic functions of ubiquitin in cell signaling. Mol. Cell 2009, 33, 275-286.
42. Duszenko, M.; Ginger, M.L.; Brennand, A.; Gualdron-Lopez, M.; Colombo, M.I.; Coombs, G.H.; Coppens, I.; Jayabalasingham, B.; Langsley, G.; de Castro, S.L.; et al. Autophagy in protists. Autophagy 2011, 7, 127-158.
43. Kirkin, V.; McEwan, D.G.; Novak, I.; Dikic, I. A role for ubiquitin in selective autophagy. Mol. Cell 2009, 34, 259-269.
44. Yang, Z.; Klionsky, D.J. Eaten alive: A history of macroautophagy. Nat. Cell Biol. 2010, 12, 814-822.
45. Yoshimoto, K.; Takano, Y.; Sakai, Y. Autophagy in plants and phytopathogens. FEBS Lett. 2010, 584, 1350-1358.
46. Mizushima, N. Autophagy: Process and function. Gene Dev. 2007, 21, 2861-2873.
47. Kamada, Y.; Funakoshi, T.; Shintani, T.; Nagano, K.; Ohsumi, M.; Ohsumi, Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J. Cell Biol. 2000, 150, 1507-1513.
48. Kihara, A.; Noda, T.; Ishihara, N.; Ohsumi, Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell Biol. 2001, 152, 519-530.
49. Noda, T.; Kim, J.; Huang, W.P.; Baba, M.; Tokunaga, C.; Ohsumi, Y.; Klionsky, D.J. Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways. J. Cell Biol. 2000, 148, 465-480.
50. Kuma, A.; Mizushima, N.; Ishihara, N.; Ohsumi, Y. Formation of the approximately 350-kDa Apg12-Apg5. Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J. Biol. Chem. 2002, 277, 18619-18625.
51. Hanada, T.; Noda, N.N.; Satomi, Y.; Ichimura, Y.; Fujioka, Y.; Takao, T.; Inagaki, F.; Ohsumi, Y. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J. Biol. Chem. 2007, 282, 37298-37302.
52. Kirisako, T.; Baba, M.; Ishihara, N.; Miyazawa, K.; Ohsumi, M.; Yoshimori, T.; Noda, T.; Ohsumi, Y. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J. Cell Biol. 1999, 147, 435-446.
53. Herman, M.; Gillies, S.; Michels, P.A.; Rigden, D.J. Autophagy and related processes in trypanosomatids: Insights from genomic and bioinformatic analyses. Autophagy 2006, 2, 107-118.
54. Rigden, D.J.; Michels, P.A.; Ginger, M.L. Autophagy in protists: Examples of secondary loss, lineage-specific innovations, and the conundrum of remodeling a single mitochondrion. Autophagy 2009, 5, 784-794.
55. Barquilla, A.; Crespo, J.L.; Navarro, M. Rapamycin inhibits trypanosome cell growth by preventing TOR complex 2 formation. Proc. Natl. Acad. Sci. USA 2008, 105, 14579-14584.
56. Madeira da Silva, L.; Beverley, S.M. Expansion of the target of rapamycin (TOR) kinase family and function in Leishmania shows that TOR3 is required for acidocalcisome biogenesis and animal infectivity. Proc. Natl. Acad. Sci. USA 2010, 107, 11965-11970.
57. Alvarez, V.E.; Kosec, G.; Sant'Anna, C.; Turk, V.; Cazzulo, J.J.; Turk, B. Autophagy is involved in nutritional stress response and differentiation in Trypanosoma cruzi. J. Biol. Chem. 2008, 283, 3454-3464.
58. Brennand, A.; Gualdron-Lopez, M.; Coppens, I.; Rigden, D.J.; Ginger, M.L.; Michels, P.A. Autophagy in parasitic protists: Unique features and drug targets. Mol. Biochem. Parasit. 2011, 177, 83-99.
59. Williams, R.A.; Woods, K.L.; Juliano, L.; Mottram, J.C.; Coombs, G.H. Characterization of unusual families of ATG8-like proteins and ATG12 in the protozoan parasite Leishmania major. Autophagy 2009, 5, 159-172.
60. Li, F.J.; Shen, Q.; Wang, C.; Sun, Y.; Yuan, A.Y.; He, C.Y. A role of autophagy in Trypanosoma brucei cell death. Cell Microbiol. 2012, 14, 1242-1256.
61. Koopmann, R.; Muhammad, K.; Perbandt, M.; Betzel, C.; Duszenko, M. Trypanosoma brucei ATG8: Structural insights into autophagic-like mechanisms in protozoa. Autophagy 2009, 5, 1085-1091.
62. Hall, B.S.; Gabernet-Castello, C.; Voak, A.; Goulding, D.; Natesan, S.K.; Field, M.C. TbVps34, the trypanosome orthologue of Vps34, is required for Golgi complex segregation. J. Biol. Chem. 2006, 281, 27600-27612.
63. Vickerman, K.; Tetley, L. Recent ultrastructural studies on trypanosomes. Annales de la Societe belge de medecine tropicale 1977, 57, 441-457.
64. Opperdoes, F.R.; Borst, P. Localization of nine glycolytic enzymes in a microbody-like organelle in Trypanosoma brucei: The glycosome. FEBS Lett. 1977, 80, 360-364.
65. Galland, N.; Michels, P.A. 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. Eur. J. Cell Biol. 2010, 89, 621-637.
66. Moyersoen, J.; Choe, J.; Fan, E.; Hol, W.G.; Michels, P.A. Biogenesis of peroxisomes and glycosomes: Trypanosomatid glycosome assembly is a promising new drug target. FEMS Microbiol. Rev. 2004, 28, 603-643.
67. Bakker, B.M.; Mensonides, F.I.; Teusink, B.; van Hoek, P.; Michels, P.A.; Westerhoff, H.V. Compartmentation protects trypanosomes from the dangerous design of glycolysis. Proc. Natl. Acad. Sci. USA2000, 97, 2087-2092.
68. Herman, M.; Perez-Morga, D.; Schtickzelle, N.; Michels, P.A. Turnover of glycosomes during life-cycle differentiation of Trypanosoma brucei. Autophagy 2008, 4, 294-308.
69. Sakai, Y.; Oku, M.; van der Klei, I.J.; Kiel, J.A. Pexophagy: Autophagic degradation of peroxisomes. Biochim. Biophys. Acta 2006, 1763, 1767-1775.
70. Besteiro, S.; Williams, R.A.; Morrison, L.S.; Coombs, G.H.; Mottram, J.C. Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major. J. Biol. Chem. 2006, 281, 11384-11396.
71. Williams, R.A.; Tetley, L.; Mottram, J.C.; Coombs, G.H. Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana. Mol. Microbiol. 2006, 61, 655-674.
72. Goldshmidt, H.; Matas, D.; Kabi, A.; Carmi, S.; Hope, R.; Michaeli, S. Persistent ER stress induces the spliced leader RNA silencing pathway (SLS), leading to programmed cell death in Trypanosoma brucei. PLoS Pathog. 2010, 6, e1000731.
73. Brennand, A.; Rico, E.; Rigden, D.J.; Van Der Smissen, P.; Courtoy, P.; Michels, P.A.M. Trypanosoma brucei ATG24 is involved in endocytosis and autophagy. de Duve Institute, Université catholique de Louvain, Brussels, Belgium. Unpublished work, 2012.
74. Wullschleger, S.; Loewith, R.; Hall, M.N. TOR signaling in growth and metabolism. Cell 2006, 124, 471-484.
75. Loewith, R.; Hall, M.N. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 2011, 189, 1177-1201.
76. Barquilla, A.; Navarro, M. Trypanosome TOR as a major regulator of cell growth and autophagy. Autophagy 2009, 5, 256-258.
77. Denninger, V.; Koopmann, R.; Muhammad, K.; Barth, T.; Bassarak, B.; Schonfeld, C.; Kilunga, B.K.; Duszenko, M. Kinetoplastida: Model organisms for simple autophagic pathways? Meth. Enzymol. 2008, 451, 373-408.
78. Diaz-Gonzalez, R.; Kuhlmann, F.M.; Galan-Rodriguez, C.; Madeira da Silva, L.; Saldivia, M.; Karver, C.E.; Rodriguez, A.; Beverley, S.M.; Navarro, M.; Pollastri, M.P. The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing. PLoS Neglect. Trop. D. 2011, 5, e1297.
79. Uzcategui, N.L.; Carmona-Gutierrez, D.; Denninger, V.; Schoenfeld, C.; Lang, F.; Figarella, K.; Duszenko, M. Antiproliferative effect of dihydroxyacetone on Trypanosoma brucei bloodstream forms: Cell cycle progression, subcellular alterations, and cell death. Antimicrob. Agents Chemother. 2007, 51, 3960-3968.
80. Uzcategui, N.L.; Denninger, V.; Merkel, P.; Schoenfeld, C.; Figarella, K.; Duszenko, M. Dihydroxyacetone induced autophagy in African trypanosomes. Autophagy 2007, 3, 626-629.
81. Campos-Salinas, J.; Gonzalez-Rey, E. Autophagy and neuropeptides at the crossroad for parasites: To survive or to die? Autophagy 2009, 5, 551-554.
82. Delgado, M.; Anderson, P.; Garcia-Salcedo, J.A.; Caro, M.; Gonzalez-Rey, E. Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death. Cell Death Differ. 2009, 16, 406-416.
83. Cunha-e-Silva, N.; Sant'Anna, C.; Pereira, M.G.; Porto-Carreiro, I.; Jeovanio, A.L.; de Souza, W. Reservosomes: Multipurpose organelles? Parasitol. Res. 2006, 99, 325-327.
84. Alvarez, V.E.; Niemirowicz, G.T.; Cazzulo, J.J. The peptidases of Trypanosoma cruzi: Digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death. Biochim. Biophys. Acta 2011, 1824, 195-206.
85. Cazzulo, J.J.; Stoka, V.; Turk, V. Cruzipain, the major cysteine proteinase from the protozoan parasite Trypanosoma cruzi. Biol. Chem. 1997, 378, 1-10.
86. Schoijet, A.C.; Miranda, K.; Girard-Dias, W.; de Souza, W.; Flawia, M.M.; Torres, H.N.; Docampo, R.; Alonso, G.D. A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis. J. Biol. Chem. 2008, 283, 31541-31550.
87. Braga, M.V.; de Souza, W. Effects of protein kinase and phosphatidylinositol-3 kinase inhibitors on growth and ultrastructure of Trypanosoma cruzi. FEMS Microbiol. Lett. 2006, 256, 209-216.
88. Santa-Rita, R.M.; Lira, R.; Barbosa, H.S.; Urbina, J.A.; de Castro, S.L. Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): Cellular and ultrastructural analysis. J. Antimicrob. Chemoth. 2005, 55, 780-784.
89. Fernandes, M.C.; Da Silva, E.N.; Pinto, A.V.; De Castro, S.L.; Menna-Barreto, R.F. A novel triazolic naphthofuranquinone induces autophagy in reservosomes and impairment of mitosis in Trypanosoma cruzi. Parasitology 2012, 139, 26-36.
90. Menna-Barreto, R.F.; Correa, J.R.; Cascabulho, C.M.; Fernandes, M.C.; Pinto, A.V.; Soares, M.J.; De Castro, S.L. Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi. Parasitology 2009, 136, 499-510.
91. Menna-Barreto, R.F.; Correa, J.R.; Pinto, A.V.; Soares, M.J.; de Castro, S.L. Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from beta-lapachone. Parasitol. Res. 2007, 101, 895-905.
92. Menna-Barreto, R.F.; Henriques-Pons, A.; Pinto, A.V.; Morgado-Diaz, J.A.; Soares, M.J.; De Castro, S.L. Effect of a beta-lapachone-derived naphthoimidazole on Trypanosoma cruzi: Identification of target organelles. J. Antimicrob. Chemoth. 2005, 56, 1034-1041.
93. Codogno, P.; Meijer, A.J. Atg5: More than an autophagy factor. Nat. Cell Biol. 2006, 8, 1045-1047.
94. Besteiro, S.; Williams, R.A.; Coombs, G.H.; Mottram, J.C. Protein turnover and differentiation in Leishmania. Int. J. Parasitol. 2007, 37, 1063-1075.
95. Cloutier, S.; Laverdiere, M.; Chou, M.N.; Boilard, N.; Chow, C.; Papadopoulou, B. Translational control through eIF2alpha phosphorylation during the leishmania differentiation process. PLoS One 2012, 7, e35085.
96. McConville, M.J.; Naderer, T. Metabolic pathways required for the intracellular survival of Leishmania. Annu. Rev. Microbiol. 2011, 65, 543-561.
97. Saunders, E.C.; DP, D.E.S.; Naderer, T.; Sernee, M.F.; Ralton, J.E.; Doyle, M.A.; Macrae, J.I.; Chambers, J.L.; Heng, J.; Nahid, A.; et al. Central carbon metabolism of Leishmania parasites. Parasitology 2010, 137, 1303-1313.
98. Coombs, G.H.; Tetley, L.; Moss, V.A.; Vickerman, K. Three dimensional structure of the Leishmania amastigote as revealed by computer-aided reconstruction from serial sections. Parasitology 1986, 92, 13-23.
99. Hart, D.T.; Opperdoes, F.R. The occurrence of glycosomes (microbodies) in the promastigote stage of four major Leishmania species. Mol. Biochem. Parasit. 1984, 13, 159-172.
100. Waller, R.F.; McConville, M.J. Developmental changes in lysosome morphology and function Leishmania parasites. Int. J. Parasitol. 2002, 32, 1435-1445.
101. Williams, R.A.; Smith, T.K.; Cull, B.; Mottram, J.C.; Coombs, G.H. ATG5 Is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major. PLoS Pathog. 2012, 8, e1002695.
102. Bhattacharya, A.; Biswas, A.; Das, P.K. Identification of a protein kinase A regulatory subunit from Leishmania having importance in metacyclogenesis through induction of autophagy. Mol. Microbiol. 2012, 83, 548-564.
103. Schurigt, U.; Schad, C.; Glowa, C.; Baum, U.; Thomale, K.; Schnitzer, J.K.; Schultheis, M.; Schaschke, N.; Schirmeister, T.; Moll, H. Aziridine-2,3-dicarboxylate-based cysteine cathepsin inhibitors induce cell death in Leishmania major associated with accumulation of debris in autophagy-related lysosome-like vacuoles. Antimicrob. Agents Chemother. 2010, 54, 5028-5041.
104. Monte Neto, R.L.; Sousa, L.M.; Dias, C.S.; Barbosa Filho, J.M.; Oliveira, M.R.; Figueiredo, R.C. Morphological and physiological changes in Leishmania promastigotes induced by yangambin, a lignan obtained from Ocotea duckei. Exp. Parasitol. 2011, 127, 215-221.
105. de Macedo-Silva, S.T.; de Oliveira Silva, T.L.; Urbina, J.A.; de Souza, W.; Rodrigues, J.C. Antiproliferative, ultrastructural, and physiological effects of amiodarone on promastigote and amastigote forms of leishmania amazonensis. Mol. Biol. Int. 2011, 2011, 876021.
106. Bera, A.; Singh, S.; Nagaraj, R.; Vaidya, T. Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides. Mol. Biochem. Parasit. 2003, 127, 23-35.
107. Romano, P.S.; Arboit, M.A.; Vazquez, C.L.; Colombo, M.I. The autophagic pathway is a key component in the lysosomal dependent entry of Trypanosoma cruzi into the host cell. Autophagy 2009, 5, 6-18.
108. Chonghaile, T.N.; Letai, A. Who put the "A" in Atg12: Autophagy or apoptosis? Mol. Cell 2011, 44, 844-845.
109. Rubinstein, A.D.; Eisenstein, M.; Ber, Y.; Bialik, S.; Kimchi, A. The autophagy protein Atg12 associates with antiapoptotic Bcl-2 family members to promote mitochondrial apoptosis. Mol. Cell 2011, 44, 698-709.
110. Fulda, S. Autophagy and cell death. Autophagy 2012, 8, in press.
111. Sengupta, S.; Chowdhury, S.; Bosedasgupta, S.; Wright, C.W.; Majumder, H.K. Cryptolepine-induced cell death of leishmania donovani promastigotes is augmented by inhibition of autophagy. Mol. Biol. Int. 2011, 2011, 187850.
112. Paugam, A.; Bulteau, A.L.; Dupouy-Camet, J.; Creuzet, C.; Friguet, B. Characterization and role of protozoan parasite proteasomes. Trends Parasitol. 2003, 19, 55-59.
113. Robertson, C.D. The Leishmania mexicana proteasome. Mol. Biochem. Parasitol. 1999, 103, 49-60.
114. Nkemngu, N.J.; Rosenkranz, V.; Wink, M.; Steverding, D. Antitrypanosomal activities of proteasome inhibitors. Antimicrob. Agents Chemother. 2002, 46, 2038-2040.
115. King, J.S. Autophagy across the eukaryotes: Is S. cerevisiae the odd one out? Autophagy 2012, 8, in press.
116. Veiga-Santos, P.; Barrias, E.S.; Santos, J.F.; de Barros Moreira, T.L.; de Carvalho, T.M.; Urbina, J.A.; de Souza, W. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int. J. Antimicrob. Agents 2012, 40, 61-71.