ArticlePLoS biology2020
Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Conserved and divergent mitochondrial assemblies in kinetoplastid parasites.Molecular cell · 2026Article
- Identification of a conserved gene family with an essential role inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dissecting Metabolic Rewiring and Gene-Metabolite Interactions by Utilizing Untargeted Metabolomics and Single-Gene Knockouts in the Model MicroorganismJournal of the American Society for Mass Spectrometry · 2026Article
- Reversal of ATP synthase is a key attribute accompanying cellular differentiation of Trypanosoma brucei insect forms.Communications biology · 2026Article
- A factor integrating transcription and repression of surface antigen genes in African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biochemistry of Diplonemids.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Kinetoplast DNA structure, RNA editing patterns and small respiratory Complex I in Trypanosoma musculi.Communications biology · 2025Article
- Cytological profiling of trypanocidal principles fromPhytomedicine plus : international journal of phytotherapy and phytopharmacology · 2025Article
- TblncRNA-23, a long non-coding RNA transcribed by RNA polymerase I, regulates developmental changes in Trypanosoma brucei.Nature communications · 2025Article
- Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications.Essays in biochemistry · 2024Review
- Multilayer omics reveals the molecular mechanism of early infection of Clonorchis sinensis juvenile.Parasites & vectors · 2023Article
- Two cold shock domain containing proteins trigger the development of infectious Trypanosoma brucei.PLoS pathogens · 2023Article
- Article
- Characterization of a highly diverged mitochondrial ATP synthase FThe Journal of biological chemistry · 2022Article
- Single-cell transcriptomics reveals expression profiles of Trypanosoma brucei sexual stages.PLoS pathogens · 2022Article
- Several different sequences are implicated in bloodstream-form-specific gene expression in Trypanosoma brucei.PLoS neglected tropical diseases · 2022Article
- Interactions of theParasitology · 2022Article
- Article
- VEX1 Influences mVSG Expression During the Transition to Mammalian Infectivity inFrontiers in cell and developmental biology · 2022Article
- The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands.PLoS pathogens · 2021Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
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 emerging concept that mitochondria act as signaling organelles through release of ROS to drive cellular differentiation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.