title: Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes.
abstract: The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
authors.affiliation: Laboratório de Biologia Celular Parasitária, Programa de Biologia Celular e Parasitologia, Instituto de Biofı́sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil1.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Vannier-Santos
authors.affiliation: Laboratório de Biologia Celular Parasitária, Programa de Biologia Celular e Parasitologia, Instituto de Biofı́sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil1.
authors.forename: Andrea
authors.initials: A
authors.lastname: Martiny
authors.affiliation: Setor de Microscopia Eletrônica e Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil2.
authors.forename: Ulysses
authors.initials: U
authors.lastname: Lins
authors.affiliation: Laboratório de Quı́mica Biológica, Instituto Venezoelano de Investigaciones Cientı́ficas-IVIC, Venezuela3.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Urbina
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofı́sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil4.
authors.forename: Valéria M
authors.initials: VM
authors.lastname: Borges
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofı́sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil4.
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D055316:Cystatin C; D015891:Cystatins / Q000032:analysis; D004577:Electron Probe Microanalysis; D006735:Horseradish Peroxidase / Q000032:analysis; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D007654:Ketoconazole / Q000494:pharmacology; D007894:Leishmania mexicana / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009281:Naphthalenes / Q000494:pharmacology; D010758:Phosphorus / Q000378:metabolism*; D013261:Sterols / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000077291:Terbinafine; D014168:Transferrin / Q000032:analysis; D014344:Trypanocidal Agents / Q000494:pharmacology
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D009281:Naphthalenes; D013261:Sterols; D014168:Transferrin; D014344:Trypanocidal Agents; D010758:Phosphorus; D006735:Horseradish Peroxidase; D000077291:Terbinafine; D007654:Ketoconazole; D002118:Calcium