Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei

PLoS Biology
Eva DoleželováAlena Zíková

Abstract

Mitochondrial metabolic remodeling is a hallmark of the Trypanosoma brucei digenetic life cycle because the insect stage utilizes a cost-effective oxidative phosphorylation (OxPhos) to generate ATP, while bloodstream cells switch to aerobic glycolysis. Due to difficulties in acquiring enough parasites from the tsetse fly vector, the dynamics of the parasite's metabolic rewiring in the vector have remained obscure. Here, we took advantage of in vitro-induced differentiation to follow changes at the RNA, protein, and metabolite levels. This multi-omics and cell-based profiling showed an immediate redirection of electron flow from the cytochrome-mediated pathway to an alternative oxidase (AOX), an increase in proline consumption, elevated activity of complex II, and certain tricarboxylic acid (TCA) cycle enzymes, which led to mitochondrial membrane hyperpolarization and increased reactive oxygen species (ROS) levels. Interestingly, these ROS molecules appear to act as signaling molecules driving developmental progression because ectopic expression of catalase, a ROS scavenger, halted the in vitro-induced differentiation. Our results provide insights into the mechanisms of the parasite's mitochondrial rewiring and reinforce the eme...Continue Reading

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Citations

Dec 15, 2020·Trends in Parasitology·Juan F QuintanaMark C Field
Feb 25, 2021·The Journal of Eukaryotic Microbiology·Tomáš BílýHassan Hashimi
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Eduardo J PatriarcaGabriella Minchiotti

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Datasets Mentioned

BETA
MTBLS1390
PRJNA381952

Methods Mentioned

BETA
RNA-Seq
electrophoresis
FACS
flow cytometry
dissections
Assay
transgenic
PCA

Software Mentioned

fastqc
fasta
STAR
fpc
R ggbiplot
dupRadar
Prism
MaxQuant
R
gplots

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