Počet záznamů: 1  

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

  1. 1.
    0537308 - BC 2021 RIV US eng J - Článek v odborném periodiku
    Doleželová, Eva - Kunzová, Michaela - Dejung, M. - Levin, M. - Panicucci, Brian - Regnault, C. - Janzen, C. J. - Barrett, M. P. - Butter, F. - Zíková, Alena
    Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei.
    PLOS Biology. Roč. 18, č. 6 (2020), č. článku e3000741. ISSN 1544-9173. E-ISSN 1545-7885
    Grant CEP: GA ČR GA17-22248S; GA MŠMT(CZ) EF16_019/0000759
    Institucionální podpora: RVO:60077344
    Klíčová slova: krebs cycle * complex-i * blood-stream * differentiation * surface * forms * dehydrogenase * expression * succinate * proteome
    Obor OECD: Microbiology
    Impakt faktor: 8.029, rok: 2020
    Způsob publikování: Open access
    https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000741

    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.
    Trvalý link: http://hdl.handle.net/11104/0315035

     
     
Počet záznamů: 1  

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