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A tryparedoxin-coupled biosensor reveals a mitochondrial trypanothione metabolism in trypanosomes.
Ebersoll, Samantha; Bogacz, Marta; Günter, Lina M; Dick, Tobias P; Krauth-Siegel, R Luise.
Afiliación
  • Ebersoll S; Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.
  • Bogacz M; Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.
  • Günter LM; Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.
  • Dick TP; Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Krauth-Siegel RL; Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.
Elife ; 92020 01 31.
Article en En | MEDLINE | ID: mdl-32003744
Trypanosoma brucei are single-celled parasites that cause human sleeping sickness and animal diseases. Like in other organisms, the parasite contains different compartments, each having several specific roles. The mitochondrion is the compartment that provides most of the energy needed to keep the cell alive. Many cellular processes, such as those that happen in the mitochondrion, produce compounds including hydrogen peroxide that can cause 'oxidative damage'. To counteract this, cells make small molecules called thiols. These thiols provide 'reducing' power to chemically balance out the oxidative damage. Trypanosomes have an unusual thiol system that relies on a molecule called trypanothione. Trypanosoma brucei cells make trypanothione in the cytosol, the fluid which surrounds all cellular compartments; here it is also used up with the help of a protein called tryparedoxin. However, it was not known which thiols are present in the mitochondrion. Ebersoll et al. have now made a molecular sensor that can detect trypanothione. The sensor includes a fluorescent protein, which changes its brightness based on its oxidation state, fused to the tryparedoxin protein. This probe could either be put in the cytosol or mitochondrion of Trypanosoma brucei cells. Treating the cells with hydrogen peroxide changed the fluorescence of the biosensor. Trypanosoma brucei cells without tryparedoxin protein in their cytosol still responded to an oxidative challenge in the mitochondrion. The experiments reveal that trypanosomes do have a mitochondrial trypanothione system. This new fluorescent biosensor will be used to study how other cellular compartments deal with oxidative conditions. The tests will reveal how different compartments communicate with each other to counteract the stress. The sensor could also be used to determine how anti-parasite drugs affect the cells' trypanothione system.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiorredoxinas / Trypanosoma brucei brucei / Espermidina / Glutatión / Mitocondrias Idioma: En Revista: Elife Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tiorredoxinas / Trypanosoma brucei brucei / Espermidina / Glutatión / Mitocondrias Idioma: En Revista: Elife Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido