Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>

ABSTRACT Trypanosoma cruzi parasites causing Chagas disease are passed between mammals by the triatomine bug vector. Within the insect, T. cruzi epimastigote-stage cells replicate and progress through the increasingly nutrient-restricted digestive tract, differentiating into infectious, nonreplicati...

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Autores principales: Aubie K. Shaw, Murat C. Kalem, Sara L. Zimmer
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Publicado: American Society for Microbiology 2016
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spelling oai:doaj.org-article:365107804793499e8445e184ca892ae02021-11-15T15:21:22ZMitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>10.1128/mSphere.00051-162379-5042https://doaj.org/article/365107804793499e8445e184ca892ae02016-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00051-16https://doaj.org/toc/2379-5042ABSTRACT Trypanosoma cruzi parasites causing Chagas disease are passed between mammals by the triatomine bug vector. Within the insect, T. cruzi epimastigote-stage cells replicate and progress through the increasingly nutrient-restricted digestive tract, differentiating into infectious, nonreplicative metacyclic trypomastigotes. Thus, we evaluated how nutrient perturbations or metacyclogenesis affects mitochondrial gene expression in different insect life cycle stages. We compared mitochondrial RNA abundances in cultures containing fed, replicating epimastigotes, differentiating cultures containing both starved epimastigotes and metacyclic trypomastigotes and epimastigote starvation cultures. We observed increases in mitochondrial rRNAs and some mRNAs in differentiating cultures. These increases predominated only for the edited CYb mRNA in cultures enriched for metacyclic trypomastigotes. For the other transcripts, abundance increases were linked to starvation and were strongest in culture fractions with a high population of starved epimastigotes. We show that loss of both glucose and amino acids results in rapid increases in RNA abundances that are quickly reduced when these nutrients are returned. Furthermore, the individual RNAs exhibit distinct temporal abundance patterns, suggestive of multiple mechanisms regulating individual transcript abundance. Finally, increases in mitochondrial respiratory complex subunit mRNA abundances were not matched by increases in abundances of nucleus-encoded subunit mRNAs, nor were there statistically significant increases in protein levels of three nucleus-encoded subunits tested. These results show that, similarly to that in T. brucei, the mitochondrial genome in T. cruzi has the potential to alter gene expression in response to environmental or developmental stimuli but for an as-yet-unknown purpose. IMPORTANCE Chagas disease is caused by insect-transmitted Trypanosoma cruzi. Halting T. cruzi’s life cycle in one of its various human and insect life stages would effectively stop the parasite’s infection cycle. T. cruzi is exposed to a variety of environmental conditions in its different life stages, and gene expression must be remodeled to survive these changes. In this work, we look at the impact that one of these changes, nutrient depletion, has on the expression of the 20 gene products encoded in the mitochondrial genome that is neglected by whole-genome studies. We show increases in mitochondrial RNA abundances in starved insect-stage cells, under two conditions in which transition to the infectious stage occurs or does not. This report is the first to show that T. cruzi mitochondrial gene expression is sensitive to environmental perturbations, consistent with mitochondrial gene expression regulatory pathways being potential antiparasitic targets.Aubie K. ShawMurat C. KalemSara L. ZimmerAmerican Society for MicrobiologyarticleKinetoplastidaRNA editingTrypanosoma cruzimRNA stabilitymitochondriaregulation of gene expressionMicrobiologyQR1-502ENmSphere, Vol 1, Iss 2 (2016)
institution DOAJ
collection DOAJ
language EN
topic Kinetoplastida
RNA editing
Trypanosoma cruzi
mRNA stability
mitochondria
regulation of gene expression
Microbiology
QR1-502
spellingShingle Kinetoplastida
RNA editing
Trypanosoma cruzi
mRNA stability
mitochondria
regulation of gene expression
Microbiology
QR1-502
Aubie K. Shaw
Murat C. Kalem
Sara L. Zimmer
Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
description ABSTRACT Trypanosoma cruzi parasites causing Chagas disease are passed between mammals by the triatomine bug vector. Within the insect, T. cruzi epimastigote-stage cells replicate and progress through the increasingly nutrient-restricted digestive tract, differentiating into infectious, nonreplicative metacyclic trypomastigotes. Thus, we evaluated how nutrient perturbations or metacyclogenesis affects mitochondrial gene expression in different insect life cycle stages. We compared mitochondrial RNA abundances in cultures containing fed, replicating epimastigotes, differentiating cultures containing both starved epimastigotes and metacyclic trypomastigotes and epimastigote starvation cultures. We observed increases in mitochondrial rRNAs and some mRNAs in differentiating cultures. These increases predominated only for the edited CYb mRNA in cultures enriched for metacyclic trypomastigotes. For the other transcripts, abundance increases were linked to starvation and were strongest in culture fractions with a high population of starved epimastigotes. We show that loss of both glucose and amino acids results in rapid increases in RNA abundances that are quickly reduced when these nutrients are returned. Furthermore, the individual RNAs exhibit distinct temporal abundance patterns, suggestive of multiple mechanisms regulating individual transcript abundance. Finally, increases in mitochondrial respiratory complex subunit mRNA abundances were not matched by increases in abundances of nucleus-encoded subunit mRNAs, nor were there statistically significant increases in protein levels of three nucleus-encoded subunits tested. These results show that, similarly to that in T. brucei, the mitochondrial genome in T. cruzi has the potential to alter gene expression in response to environmental or developmental stimuli but for an as-yet-unknown purpose. IMPORTANCE Chagas disease is caused by insect-transmitted Trypanosoma cruzi. Halting T. cruzi’s life cycle in one of its various human and insect life stages would effectively stop the parasite’s infection cycle. T. cruzi is exposed to a variety of environmental conditions in its different life stages, and gene expression must be remodeled to survive these changes. In this work, we look at the impact that one of these changes, nutrient depletion, has on the expression of the 20 gene products encoded in the mitochondrial genome that is neglected by whole-genome studies. We show increases in mitochondrial RNA abundances in starved insect-stage cells, under two conditions in which transition to the infectious stage occurs or does not. This report is the first to show that T. cruzi mitochondrial gene expression is sensitive to environmental perturbations, consistent with mitochondrial gene expression regulatory pathways being potential antiparasitic targets.
format article
author Aubie K. Shaw
Murat C. Kalem
Sara L. Zimmer
author_facet Aubie K. Shaw
Murat C. Kalem
Sara L. Zimmer
author_sort Aubie K. Shaw
title Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_short Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_full Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_fullStr Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_full_unstemmed Mitochondrial Gene Expression Is Responsive to Starvation Stress and Developmental Transition in <named-content content-type="genus-species">Trypanosoma cruzi</named-content>
title_sort mitochondrial gene expression is responsive to starvation stress and developmental transition in <named-content content-type="genus-species">trypanosoma cruzi</named-content>
publisher American Society for Microbiology
publishDate 2016
url https://doaj.org/article/365107804793499e8445e184ca892ae0
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