The Adaptability of the T. brucei Bloodstream Mitochondria upon the Indirect Knockdown of an Essential Mitochondrially Encoded Protein

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F14%3A00488312" target="_blank" >RIV/60077344:_____/14:00488312 - isvavai.cz</a>

Result on the web

<a href="http://www.parazitologie.cz/protozoologie/Protodny2014/JPD_sbornik_2014.pdf" target="_blank" >http://www.parazitologie.cz/protozoologie/Protodny2014/JPD_sbornik_2014.pdf</a>

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

The Adaptability of the T. brucei Bloodstream Mitochondria upon the Indirect Knockdown of an Essential Mitochondrially Encoded Protein

Original language description

The infective bloodstream stage 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 membrane potential. Due to this reduced organellar function, it is currently presumed that out of the 18 mitochondrially (mt) encoded proteins, only A6 (a subunit of FoF1-ATPase) and possibly RPS12 (a ribosomal subunit) are essential in BF trypanosomes. We have identified the hypothetical mt matrix protein TbMT420 as a homologue to a yeast methyltransferase (Mtq1) that methylates a conserved GGQ motif of the peptide release factor 1 (Mrf1). Therefore, we generated viable knock-out cell lines to explore these components of the mt translation machinery in T. brucei. The ΔTbMrf1 cell line possesses a decreased mt membrane potential, an increased sensitivity to FoF1 inhibitors, and a decreased abundance of the FoF1-ATPase complex. However, the ^ITbMT420 cells exhibit milder phenotypes, suggesting that the methylation is not as influential as the loss of TbMrf1. We conclude that the loss of TbMrf1 leads to significantly less functional A6 and possibly RPS12, but enough FoF1-ATPase is still assembled to maintain a sufficient membrane potential. Interestingly, over time the phenotypes dissipate, possibly as the cells try to compensate for the loss of A6. We are currently exploring this possibility and determining if the ΔTbMrf1 cell line is still infectious in the animal host.n

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

2014

Confidentiality

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