Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication

Trypanosoma cruzi, the causative agent of Chagas disease, presents a complex life cycle and adapts its metabolism to nutrients’ availability. Although T. cruzi is an aerobic organism, it does not produce heme. This cofactor is acquired from the host and is distributed and inserted into different hem...

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Autores principales: Merli, Marcelo Luciano, Cirulli, Brenda Analía, Menéndez-Bravo, Simón M., Cricco, Julia Alejandra
Formato: article artículo acceptedVersion
Lenguaje:Inglés
Publicado: Portland Press 2020
Materias:
Chagas disease
complex IV
heme A
heme A synthase
trypanosomes
Acceso en línea:http://hdl.handle.net/2133/18327
http://hdl.handle.net/2133/18327
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-18327
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 Chagas disease
complex IV
heme A
heme A synthase
trypanosomes
spellingShingle Chagas disease
complex IV
heme A
heme A synthase
trypanosomes
Merli, Marcelo Luciano
Cirulli, Brenda Analía
Menéndez-Bravo, Simón M.
Cricco, Julia Alejandra
Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
topic_facet Chagas disease
complex IV
heme A
heme A synthase
trypanosomes
description Trypanosoma cruzi, the causative agent of Chagas disease, presents a complex life cycle and adapts its metabolism to nutrients’ availability. Although T. cruzi is an aerobic organism, it does not produce heme. This cofactor is acquired from the host and is distributed and inserted into different heme-proteins such as respiratory complexes in the parasite's mitochondrion. It has been proposed that T. cruzi's energy metabolism relies on a branched respiratory chain with a cytochrome c oxidase-type aa3 (CcO) as the main terminal oxidase. Heme A, the cofactor for all eukaryotic CcO, is synthesized via two sequential enzymatic reactions catalyzed by heme O synthase (HOS) and heme A synthase (HAS). Previously, TcCox10 and TcCox15 (Trypanosoma cruzi Cox10 and Cox15 proteins) were identified in T. cruzi. They presented HOS and HAS activity, respectively, when they were expressed in yeast. Here, we present the first characterization of TcCox15 in T. cruzi, confirming its role as HAS. It was differentially detected in the different T. cruzi stages, being more abundant in the replicative forms. This regulation could reflect the necessity of more heme A synthesis, and therefore more CcO activity at the replicative stages. Overexpression of a non-functional mutant caused a reduction in heme A content. Moreover, our results clearly showed that this hindrance in the heme A synthesis provoked a reduction on CcO activity and, in consequence, an impairment on T. cruzi survival, proliferation and infectivity. This evidence supports that T. cruzi depends on the respiratory chain activity along its life cycle, being CcO an essential terminal oxidase.
format article
artículo
acceptedVersion
author Merli, Marcelo Luciano
Cirulli, Brenda Analía
Menéndez-Bravo, Simón M.
Cricco, Julia Alejandra
author_facet Merli, Marcelo Luciano
Cirulli, Brenda Analía
Menéndez-Bravo, Simón M.
Cricco, Julia Alejandra
author_sort Merli, Marcelo Luciano
title Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
title_short Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
title_full Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
title_fullStr Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
title_full_unstemmed Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
title_sort heme a synthesis and cco activity are essential for trypanosoma cruzi infectivity and replication
publisher Portland Press
publishDate 2020
url http://hdl.handle.net/2133/18327
http://hdl.handle.net/2133/18327
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AT cirullibrendaanalia hemeasynthesisandccoactivityareessentialfortrypanosomacruziinfectivityandreplication
AT menendezbravosimonm hemeasynthesisandccoactivityareessentialfortrypanosomacruziinfectivityandreplication
AT criccojuliaalejandra hemeasynthesisandccoactivityareessentialfortrypanosomacruziinfectivityandreplication
bdutipo_str Repositorios
_version_ 1764820410235355140

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