%0 Journal Article
%T Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei
%A Alena Z¨ªkov¨¢
%A Brian Panicucci
%A Christian J. Janzen
%A Cl¨¦ment Regnault
%A Eva Dole£¿elov¨¢
%A Falk Butter
%A Mario Dejung
%A Michael P. Barrett
%A Michaela Kunzov¨¢
%A Michal Levin
%J PLOS Biology: A Peer-Reviewed Open-Access Journal
%D 2020
%R 10.1371/journal.pbio.3000741
%X 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¨Cinduced 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¨Cinduced 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
%K Mitochondria
%K Cell differentiation
%K Trypanosoma
%K Trypanosoma brucei gambiense
%K Proline
%K Epimastigotes
%K RNA-binding proteins
%K Protein metabolism
%U https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000741