Journal Article

Glycerol suppresses glucose consumption in trypanosomes through metabolic contest

Tetaud, Emmanuel, Portais, Jean-Charles, Allmann, Stefan, STROMALab, Rivière, Loïc, Villafraz, Oriana, Cahoreau, Edern, ANR-15-CE15-0025, GLYCONOV,Voies métaboliques glycosomales non glycolytiques: nouvelles fonctions pour le développement et la virulence des trypanosomes, Asencio, Corinne, Bringaud, Frédéric, MetaToul FluxoMet (TBI-MetaToul), Rotureau, Brice, Plazolles, Nicolas, MetaboHUB-Génopole Toulouse Midi-Pyrénées (GENOTOUL), Wargnies, Marion, ANR-19-CE15-0004, AdipoTryp,Interactions métaboliques entre les adipocytes et les trypanosomes, un nouveau paradigme pour les trypanosomoses, Kulyk, Hanna, Biologie cellulaire des Trypanosomes - Trypanosome Cell Biology, MetaboHUB-MetaToul, Morand, Pauline, Pineda, Erika, Mourier, Arnaud, Biran, Marc, Microbiologie Fondamentale et Pathogénicité (MFP)

2021

Overview

Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, known as “catabolite repression,” allowing redirection of cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism named “metabolic contest” for regulating the use of carbon sources without nutrient sensing and signaling. Trypanosoma brucei is a unicellular eukaryote transmitted by tsetse flies and causing human African trypanosomiasis, or sleeping sickness. We showed that, in contrast to most microorganisms, the insect stages of this parasite developed a preference for glycerol over glucose, with glucose consumption beginning after the depletion of glycerol present in the medium. This “metabolic contest” depends on the combination of 3 conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-related organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways both being ATP-dependent (glycerol kinase and hexokinase, respectively); and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being approximately 80-fold higher than the hexokinase activity. As predicted by our model, an approximately 50-fold down-regulation of the GK expression abolished the preference for glycerol over glucose, with glucose and glycerol being metabolized concomitantly. In theory, a metabolic contest could be found in any organism provided that the 3 conditions listed above are met.

• Publisher: CCSD,Public Library of Science,Public Library of Science (PLoS)
• Subject: African trypanosomiasis / Analysis / ATP / Biology and Life Sciences / Carbon / Carbon sources / Catabolite repression / Changing environments / Chromatography / Consumption / Depletion / Energy efficiency / Energy transfer / Environmental changes / Enzymes / Glucose / Glucose metabolism / Glycerin / Glycerol / Glycerol kinase / Glycosomes / Hexokinase / Identification and classification / Insects / Kinases / Life Sciences / Mass spectrometry / Metabolic pathways / Metabolism / Metabolites / Microbiology and Parasitology / Microorganisms / NMR / Nuclear magnetic resonance / Nutrient sources / Organelles / Parasites / Parasitology / Phosphates / Phosphorylation / Physical Sciences / Physiological aspects / Properties / Proteins / Regulatory mechanisms (biology) / Research and Analysis Methods / Scientific imaging / Signal transduction / Signaling / Substrates / Trypanosoma / Vector-borne diseases / Yeast / Yeasts
• ISBN: 9780006847113, 0006847110