Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>

ABSTRACT Amino acids participate in several critical processes in the biology of trypanosomatids, such as osmoregulation, cell differentiation, and host cell invasion. Some of them provide reducing power for mitochondrial ATP synthesis. It was previously shown that alanine, which is formed mainly by...

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Autores principales: Richard M. B. M. Girard, Marcell Crispim, Mayke Bezerra Alencar, Ariel Mariano Silber
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:a3111519d69f4390bcbb0fd595403c5a2021-11-15T15:25:50ZUptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>10.1128/mSphereDirect.00338-182379-5042https://doaj.org/article/a3111519d69f4390bcbb0fd595403c5a2018-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00338-18https://doaj.org/toc/2379-5042ABSTRACT Amino acids participate in several critical processes in the biology of trypanosomatids, such as osmoregulation, cell differentiation, and host cell invasion. Some of them provide reducing power for mitochondrial ATP synthesis. It was previously shown that alanine, which is formed mainly by the amination of pyruvate, is a metabolic end product formed when parasites are replicating in a medium rich in glucose and amino acids. It was shown as well that this amino acid can also be used for the regulation of cell volume and resistance to osmotic stress. In this work, we demonstrate that, despite it being an end product of its metabolism, Trypanosoma cruzi can take up and metabolize l-Ala through a low-specificity nonstereoselective active transport system. The uptake was dependent on the temperature in the range between 10 and 40°C, which allowed us to calculate an activation energy of 66.4 kJ/mol and estimate the number of transporters per cell at ~436,000. We show as well that, once taken up by the cells, l-Ala can be completely oxidized to CO2, supplying electrons to the electron transport chain, maintaining the electrochemical proton gradient across the mitochondrial inner membrane, and supporting ATP synthesis in T. cruzi epimastigotes. Our data demonstrate a dual role for Ala in the parasite’s bioenergetics, by being a secreted end product of glucose catabolism and taken up as nutrient for oxidative mitochondrial metabolism. IMPORTANCE It is well known that trypanosomatids such as the etiological agent of Chagas’ disease, Trypanosoma cruzi, produce alanine as a main end product of their energy metabolism when they grow in a medium containing glucose and amino acids. In this work, we investigated if under starvation conditions (which happen during the parasite life cycle) the secreted alanine could be recovered from the extracellular medium and used as an energy source. Herein we show that indeed, in parasites submitted to metabolic stress, this metabolite can be taken up and used as an energy source for ATP synthesis, allowing the parasite to extend its survival under starvation conditions. The obtained results point to a dual role for Ala in the parasite’s bioenergetics, by being a secreted end product of glucose catabolism and taken up as nutrient for oxidative mitochondrial metabolism.Richard M. B. M. GirardMarcell CrispimMayke Bezerra AlencarAriel Mariano SilberAmerican Society for MicrobiologyarticleChagas diseasel-alanine metabolisml-alanine uptakeTrypanosoma cruzibioenergeticsMicrobiologyQR1-502ENmSphere, Vol 3, Iss 4 (2018)
institution DOAJ
collection DOAJ
language EN
topic Chagas disease
l-alanine metabolism
l-alanine uptake
Trypanosoma cruzi
bioenergetics
Microbiology
QR1-502
spellingShingle Chagas disease
l-alanine metabolism
l-alanine uptake
Trypanosoma cruzi
bioenergetics
Microbiology
QR1-502
Richard M. B. M. Girard
Marcell Crispim
Mayke Bezerra Alencar
Ariel Mariano Silber
Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
description ABSTRACT Amino acids participate in several critical processes in the biology of trypanosomatids, such as osmoregulation, cell differentiation, and host cell invasion. Some of them provide reducing power for mitochondrial ATP synthesis. It was previously shown that alanine, which is formed mainly by the amination of pyruvate, is a metabolic end product formed when parasites are replicating in a medium rich in glucose and amino acids. It was shown as well that this amino acid can also be used for the regulation of cell volume and resistance to osmotic stress. In this work, we demonstrate that, despite it being an end product of its metabolism, Trypanosoma cruzi can take up and metabolize l-Ala through a low-specificity nonstereoselective active transport system. The uptake was dependent on the temperature in the range between 10 and 40°C, which allowed us to calculate an activation energy of 66.4 kJ/mol and estimate the number of transporters per cell at ~436,000. We show as well that, once taken up by the cells, l-Ala can be completely oxidized to CO2, supplying electrons to the electron transport chain, maintaining the electrochemical proton gradient across the mitochondrial inner membrane, and supporting ATP synthesis in T. cruzi epimastigotes. Our data demonstrate a dual role for Ala in the parasite’s bioenergetics, by being a secreted end product of glucose catabolism and taken up as nutrient for oxidative mitochondrial metabolism. IMPORTANCE It is well known that trypanosomatids such as the etiological agent of Chagas’ disease, Trypanosoma cruzi, produce alanine as a main end product of their energy metabolism when they grow in a medium containing glucose and amino acids. In this work, we investigated if under starvation conditions (which happen during the parasite life cycle) the secreted alanine could be recovered from the extracellular medium and used as an energy source. Herein we show that indeed, in parasites submitted to metabolic stress, this metabolite can be taken up and used as an energy source for ATP synthesis, allowing the parasite to extend its survival under starvation conditions. The obtained results point to a dual role for Ala in the parasite’s bioenergetics, by being a secreted end product of glucose catabolism and taken up as nutrient for oxidative mitochondrial metabolism.
format article
author Richard M. B. M. Girard
Marcell Crispim
Mayke Bezerra Alencar
Ariel Mariano Silber
author_facet Richard M. B. M. Girard
Marcell Crispim
Mayke Bezerra Alencar
Ariel Mariano Silber
author_sort Richard M. B. M. Girard
title Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_short Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_full Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_fullStr Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_full_unstemmed Uptake of <sc>l</sc>-Alanine and Its Distinct Roles in the Bioenergetics of <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_sort uptake of <sc>l</sc>-alanine and its distinct roles in the bioenergetics of <named-content content-type="genus-species">trypanosoma cruzi</named-content>
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/a3111519d69f4390bcbb0fd595403c5a
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