A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
| Autor: | Lucas Pagura, Evelyn Tevere, Marcelo Luciano Merli, Julia A. Cricco |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Heme Transport Trypanosoma cruzi Protozoan Proteins Heme Biochemistry Microbiology Models Biological Cofactor 03 medical and health sciences chemistry.chemical_compound parasitic diseases Humans Homeostasis Chagas Disease Parasites Amastigote Molecular Biology Heme Responsive Gene 030102 biochemistry & molecular biology biology Cell Biology biology.organism_classification Heme transport Cell biology 030104 developmental biology chemistry Membrane protein biology.protein Function (biology) Intracellular |
| Zdroj: | RepHipUNR (UNR) Universidad Nacional de Rosario instacron:UNR J Biol Chem |
| Popis: | Heme is an essential cofactor for many biological processes in aerobic organisms, which can synthesize it de novo through a conserved pathway. Trypanosoma cruzi, the etiological agent of Chagas disease, as well as other trypanosomatids relevant to human health, are heme auxotrophs, meaning they must import it from their mammalian hosts or insect vectors. However, how these species import and regulate heme levels is not fully defined yet. It is known that the membrane protein TcHTE is involved in T. cruzi heme transport, although its specific role remains unclear. In the present work, we studied endogenous TcHTE in the different life cycle stages of the parasite to gain insight into its function in heme transport and homeostasis. We have confirmed that TcHTE is predominantly detected in repli cative stages (epimastigote and amastigote), in which heme transport activity was previously validated. We also showed that in epimastigotes, TcHTE protein and mRNA levels decrease in response to increments in heme concentration, confirming it as a member of the heme response gene family. Finally, we demon strated that T. cruzi epimastigotes can sense intracellular heme by an unknown mechanism and regulate heme transport to adapt to changing conditions. Based on these results, we pro pose a model in which T. cruzi senses intracellular heme and regulates heme transport activity by adjusting the expression of TcHTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding of a critical pathway for T. cruzi biology allowing the identification of novel and essential proteins. This is a post-peer-review, pre-copyedit version of an article published in Journal of Biological Chemistry (JBC). The final authenticated version is available online at: https://doi.org/10.1074/jbc.ra120.014574 Fil: Pagura, Lucas. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Tevere, Evelyn. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Merli, Marcelo Luciano. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina. Fil: Cricco, Julia Alejandra. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Biológica. Área Biofísica; Argentina. |
| Databáze: | OpenAIRE |
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