A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression
Archivos
Fecha
2020-07-23
Título de la revista
ISSN de la revista
Título del volumen
Editor
American Society for Biochemistry and Molecular Biology
Resumen
Descripción
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
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
Palabras clave
Trypanosoma cruzi, Chagas Disease, Heme Responsive Gene, Heme Transport, Homeostasis, Parasites