Role of inhibitory factor IF1 during the differentiation of T. brucei

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F16%3A00488334" target="_blank" >RIV/60077344:_____/16:00488334 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.parazitologie.cz/protozoologie/Protodny2016/JPD_sbornik_2016.pdf" target="_blank" >http://www.parazitologie.cz/protozoologie/Protodny2016/JPD_sbornik_2016.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Role of inhibitory factor IF1 during the differentiation of T. brucei

Popis výsledku v původním jazyce

Trypanosoma brucei undergoes a complex life cycle as it alternates between a mammalian host and the blood-feeding insect vector, a tsetse fly. Due to the different environments, the distinct life stages differ in their energy metabolism, i.e. insect stage (procyclic cells, PF) depends on mitochondrial oxidative phosphorylation (OXPHOS) for ATP production while the bloodstream stage (BF) gains energy by aerobic glycolysis. The dramatic switch from the OXPHOS to glycolysis happens during the complex development of the PF in the tsetse fly. The molecular mechanism behind this shift is still unknown. Importantly, an induced over-expression of a differentiation factor, RNA-binding protein 6 (RBP6), results in the appearance of epimastigotes and metacyclic trypanosome in vitro (Kolev, 2012). We have established this RBP6 overexpressing cell line and the presence of the distinct cell types was verified using DAPI staining to visualize position of the kinetoplast to nuclei and by an endocytosis test. Moreover, we checked for changes in expression of subunits of respiratory complexes III and V. Interestingly, the level of T. brucei inhibitory factor 1 (TbIF1), a specific natural inhibitor of complex V, was significantly increased in the RBP6-induced cells. At the same time, we detected elevated levels of radical oxygen species (ROS) and changes in mitochondrial membrane potential. This is similar to what is reported in cancer cells, where high levels of IF1 expression inhibits ATP synthesis and creates a ROS signal that triggers the metabolic switch from OXPHOS to aerobic glycolysis. Determining how TbIF1 is regulated and what is the signaling mechanism during the trypanosome differentiation are important aims of this project.

Název v anglickém jazyce

Role of inhibitory factor IF1 during the differentiation of T. brucei

Popis výsledku anglicky

Trypanosoma brucei undergoes a complex life cycle as it alternates between a mammalian host and the blood-feeding insect vector, a tsetse fly. Due to the different environments, the distinct life stages differ in their energy metabolism, i.e. insect stage (procyclic cells, PF) depends on mitochondrial oxidative phosphorylation (OXPHOS) for ATP production while the bloodstream stage (BF) gains energy by aerobic glycolysis. The dramatic switch from the OXPHOS to glycolysis happens during the complex development of the PF in the tsetse fly. The molecular mechanism behind this shift is still unknown. Importantly, an induced over-expression of a differentiation factor, RNA-binding protein 6 (RBP6), results in the appearance of epimastigotes and metacyclic trypanosome in vitro (Kolev, 2012). We have established this RBP6 overexpressing cell line and the presence of the distinct cell types was verified using DAPI staining to visualize position of the kinetoplast to nuclei and by an endocytosis test. Moreover, we checked for changes in expression of subunits of respiratory complexes III and V. Interestingly, the level of T. brucei inhibitory factor 1 (TbIF1), a specific natural inhibitor of complex V, was significantly increased in the RBP6-induced cells. At the same time, we detected elevated levels of radical oxygen species (ROS) and changes in mitochondrial membrane potential. This is similar to what is reported in cancer cells, where high levels of IF1 expression inhibits ATP synthesis and creates a ROS signal that triggers the metabolic switch from OXPHOS to aerobic glycolysis. Determining how TbIF1 is regulated and what is the signaling mechanism during the trypanosome differentiation are important aims of this project.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LL1205" target="_blank" >LL1205: Charakterizace unikátních vlastností esenciální FoF1 ATP syntázy u původce africké spavé nemoci Trypanosoma bucei za účelem vývoje inhibitorů tohoto komplexu.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů