Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.

Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the...

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Autores principales:	Helena Castro, Susana Romao, Sandra Carvalho, Filipa Teixeira, Carla Sousa, Ana M Tomás
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4c85c06044bc40729d2c1dcacd9b32da
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spelling	oai:doaj.org-article:4c85c06044bc40729d2c1dcacd9b32da2021-11-18T06:35:20ZMitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.1932-620310.1371/journal.pone.0012607https://doaj.org/article/4c85c06044bc40729d2c1dcacd9b32da2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838623/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently.Helena CastroSusana RomaoSandra CarvalhoFilipa TeixeiraCarla SousaAna M TomásPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e12607 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Helena Castro Susana Romao Sandra Carvalho Filipa Teixeira Carla Sousa Ana M Tomás Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
description	Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently.
format	article
author	Helena Castro Susana Romao Sandra Carvalho Filipa Teixeira Carla Sousa Ana M Tomás
author_facet	Helena Castro Susana Romao Sandra Carvalho Filipa Teixeira Carla Sousa Ana M Tomás
author_sort	Helena Castro
title	Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
title_short	Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
title_full	Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
title_fullStr	Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
title_full_unstemmed	Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
title_sort	mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/4c85c06044bc40729d2c1dcacd9b32da
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Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity.

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