Accessible Requires Authentication Published by De Gruyter February 28, 2015

Detection of thiol-based redox switch processes in parasites – facts and future

Mahsa Rahbari, Kathrin Diederich, Katja Becker, R. Luise Krauth-Siegel and Esther Jortzik
From the journal Biological Chemistry

Abstract

Malaria and African trypanosomiasis are tropical diseases caused by the protozoa Plasmodium and Trypanosoma, respectively. The parasites undergo complex life cycles in the mammalian host and insect vector, during which they are exposed to oxidative and nitrosative challenges induced by the host immune system and endogenous processes. Attacking the parasite’s redox metabolism is a target mechanism of several known antiparasitic drugs and a promising approach to novel drug development. Apart from this aspect, oxidation of cysteine residues plays a key role in protein-protein interaction, metabolic responses to redox events, and signaling. Understanding the role and dynamics of reactive oxygen species and thiol switches in regulating cellular redox homeostasis is crucial for both basic and applied biomedical approaches. Numerous techniques have therefore been established to detect redox changes in parasites including biochemical methods, fluorescent dyes, and genetically encoded probes. In this review, we aim to give an insight into the characteristics of redox networks in the pathogens Plasmodium and Trypanosoma, including a comprehensive overview of the consequences of specific deletions of redox-associated genes. Furthermore, we summarize mechanisms and detection methods of thiol switches in both parasites and discuss their specificity and sensitivity.


Corresponding author: Esther Jortzik, Biochemistry and Molecular Biology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26–32, D-35392 Giessen, Germany, e-mail:
aMahsa Rahbari and Kathrin Diederich: These authors contributed equally to this work.

Acknowledgments

This work was funded by the Deutsche Forschungsgemeinschaft (JO 1085/1–2 to E.J. and the DFG Priority Program ‘Dynamics of thiol-based redox switches’ SPP 1710 to K.B. (BE 1540/23-1) and L.K.-S (KR 1242/6-1).

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Received: 2014-11-28
Accepted: 2015-2-23
Published Online: 2015-2-28
Published in Print: 2015-5-1

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