Hypothetical Trypanosoma Protein Helps to Anchor the F1-ATPase Moiety to the Mitochondrial Membrane

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F13%3A00488323" target="_blank" >RIV/60077344:_____/13:00488323 - isvavai.cz</a>

Result on the web

<a href="http://www.parazitologie.cz/protozoologie/Protodny2013/JPD_sbornik_2013.pdf" target="_blank" >http://www.parazitologie.cz/protozoologie/Protodny2013/JPD_sbornik_2013.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Hypothetical Trypanosoma Protein Helps to Anchor the F1-ATPase Moiety to the Mitochondrial Membrane

Original language description

Trypanosoma brucei is a medically important parasite that infects humans and livestock. Interestingly, the mitochondrial (mt) FoF1-ATPase activity is essential in the infectious form of this pathogen as it hydrolyzes ATP to pump protons into the mt inner membrane space to maintain the mt membrane potential (mt ΔΨ) in the absence of a traditional cytochrome mediated respiratory chain. Unlike the well conserved higher eukaryotic FoF1-ATP synthases, the T. brucei FoF1-ATP synthase contains several trypanosoma specific subunits with unknown function. One of the largest novel subunits, Tb2930 (43 kDa), is membrane-bound and localizes into monomeric and multimeric assemblies of the FoF1-ATPase. RNAi silencing of Tb2930 led to a significant decrease of the mt ΔΨ and consequently to a major growth phenotype, indicating that the FoF1-ATPase is not functioning properly even though its structural intergrity seems unchanged. To further explore the function of this protein, we silenced the expression of Tb2930 in a strain of trypanosoma lacking mitochondrial DNA (dyskinetoplastic, Dk) and thus subunit a, an essential component of the Fo moiety and proton pore. Dk cells maintain mt ΔΨ by the electrogenic exchange of ATP4-/ADP3- by the ATP/ADP carrier (AAC) and the hydrolytic activity of the F1-ATPase. The depletion of Tb2930 in Dk cells resulted in a significant growth phenotype caused by a decreased mt ΔΨ. Importantly, subfractionation of the Dk mitochondria showed that in Tb2930 knockdown cells, the F1 moiety is more loosely attached to the membrane. In conclusion, Tb2930 is responsible for connecting the F1-ATPase to the mt membrane in the absence of the Fo moiety, thus increasing the efficiency of the functional association between F1-ATPase and AAC.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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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

2013

Confidentiality

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