A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression

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...

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Autores principales: Pagura, Lucas, Tevere, Evelyn, Merli, Marcelo Luciano, Cricco, Julia Alejandra
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Trypanosoma cruzi
Chagas Disease
Heme Responsive Gene
Heme Transport
Homeostasis
Parasites
Acceso en línea:http://hdl.handle.net/2133/20478
http://hdl.handle.net/2133/20478
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-20478
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Trypanosoma cruzi
Chagas Disease
Heme Responsive Gene
Heme Transport
Homeostasis
Parasites
spellingShingle Trypanosoma cruzi
Chagas Disease
Heme Responsive Gene
Heme Transport
Homeostasis
Parasites
Pagura, Lucas
Tevere, Evelyn
Merli, Marcelo Luciano
Cricco, Julia Alejandra
A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
topic_facet Trypanosoma cruzi
Chagas Disease
Heme Responsive Gene
Heme Transport
Homeostasis
Parasites
description 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.
format article
artículo
publishedVersion
author Pagura, Lucas
Tevere, Evelyn
Merli, Marcelo Luciano
Cricco, Julia Alejandra
author_facet Pagura, Lucas
Tevere, Evelyn
Merli, Marcelo Luciano
Cricco, Julia Alejandra
author_sort Pagura, Lucas
title A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
title_short A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
title_full A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
title_fullStr A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
title_full_unstemmed A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
title_sort new model for trypanosoma cruzi heme homeostasis depends on modulation of tchte protein expression
publisher American Society for Biochemistry and Molecular Biology
publishDate 2021
url http://hdl.handle.net/2133/20478
http://hdl.handle.net/2133/20478
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