Bloodstream T. brucei Adapts to Decreased Levels of Functional FoF1-ATPase subunit A6

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F15%3A00488331" target="_blank" >RIV/60077344:_____/15:00488331 - isvavai.cz</a>

Result on the web

<a href="http://www.parazitologie.cz/protozoologie/Protodny2015/JPD_sbornik_2015.pdf" target="_blank" >http://www.parazitologie.cz/protozoologie/Protodny2015/JPD_sbornik_2015.pdf</a>

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

Bloodstream T. brucei Adapts to Decreased Levels of Functional FoF1-ATPase subunit A6

Original language description

The infective bloodstream stage (BS) of Trypanosoma brucei possesses a single mitochondrion that lacks cytochrome-containing respiratory complexes III and IV and thus employs the FoF1-ATPase to hydrolyze matrix ATP to maintain the essential mitochondrial (mt) membrane potential (m). Due to this reduced organellar function, it is currently presumed that out of the 18 (mt) encoded proteins, only A6 (a subunit of FoF1-ATPase) and possibly RPS12 (a ribosomal subunit) are essential in BS trypanosomes. However, dyskinetoplastic trypanosomes, parasites locked in the bloodstream stage because they have lost their mtDNA, have found a way to maintain their m with FoF1-ATPase lacking the A6 proton pore. To explore how BS T. brucei cope with a decrease in functional A6, we generated a double knock-out cell line for the mt peptide release factor (TbMrf1). This interference with the mt translation machinery resulted in a TbMrf1 cell line with a decreased m, a decreased abundance of the FoF1-ATPase, and an increased sensitivity to FoF1-ATPase and ATP/ADP carrier inhibitors. Furthermore, while the TbMrf1 cells are viable when cultivated in vitro, it appears that they are less virulent in the mouse model, suggesting a greater reliance on mt metabolism in vivo. Importantly, in vitro cultivation over several weeks dissipates the decreased m phenotype, perhaps as the cells adapt to the depletion of functional A6 by unknown mechanism. Recently, the release factor family protein ICT1 was described to act as a mito ribosome recycling factor in case of stalled translation in human mitochondria. The function of TbICT1 homologue in TbMrf1 background is currently investigated.

Czech name

—

Czech description

—

Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LL1205" target="_blank" >LL1205: Exploration of the unique charakters od the Trypanosoma brucei FoF1 ATP synthase complex for future drug development against african sleeping sickness.</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

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