title: Electron tomography characterization of hemoglobin uptake in Plasmodium chabaudi reveals a stage-dependent mechanism for food vacuole morphogenesis.
abstract: In the course of their intraerythrocytic development, malaria parasites incorporate and degrade massive amounts of the host cell cytoplasm. This mechanism is essential for parasite development and represents a physiological step used as target for many antimalarial drugs; nevertheless, the fine mechanisms underlying these processes in Plasmodium species are still under discussion. Here, we studied the events of hemoglobin uptake and hemozoin nucleation in the different stages of the intraerythrocytic cycle of the murine malaria parasite Plasmodium chabaudi using transmission electron tomography of cryofixed and freeze-substituted cells. The results showed that hemoglobin uptake in P. chabaudi starts at the early ring stage and is present in all developmental stages, including the schizont stage. Hemozoin nucleation occurs near the membrane of small food vacuoles. At the trophozoite stage, food vacuoles are found closely localized to cytostomal tubes and mitochondria, whereas in the schizont stage, we observed a large food vacuole located in the central portion of the parasite. Taken together, these results provide new insights into the mechanisms of hemoglobin uptake and degradation in rodent malaria parasites.
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, bloco G subsolo, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil; Centro Nacional de Biologia Estrutural e Bioimagem-Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Wendt
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, bloco G subsolo, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil; Centro Nacional de Biologia Estrutural e Bioimagem-Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rachid
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, bloco G subsolo, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil; Centro Nacional de Biologia Estrutural e Bioimagem-Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, bloco G subsolo, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ 21941-902, Brazil; Centro Nacional de Biologia Estrutural e Bioimagem-Universidade Federal do Rio de Janeiro, Brazil. Electronic address: kmiranda@biof.ufrj.br.
authors.forename: Kildare
authors.initials: K
authors.lastname: Miranda
mesh_terms: D000818:Animals; D001692:Biological Transport; D055032:Electron Microscope Tomography; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology / Q000648:ultrastructure; D006420:Hemeproteins / Q000378:metabolism* / Q000648:ultrastructure; D006454:Hemoglobins / Q000378:metabolism* / Q000648:ultrastructure; D007091:Image Processing, Computer-Assisted; D008018:Life Cycle Stages / Q000502:physiology*; D008288:Malaria / Q000469:parasitology; D008297:Male; D051379:Mice; D016788:Plasmodium chabaudi / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D059748:Proteolysis; D014617:Vacuoles / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D006420:Hemeproteins; D006454:Hemoglobins; C020753:hemozoin
keywords: Electron tomography; Freeze substitution; Hemozoin; High-pressure freezing; Plasmodium; Rodent malaria; Three-dimensional reconstruction