Despite a 50% decrease in malaria infections between 2000 and 2010, malaria is still one of the three leading infectious diseases with an estimated 216 million cases worldwide in 2010. More than 90% of all malaria infections were caused by Plasmodium falciparum, a unicellular eukaryotic parasite that faces oxidative stress challenges while developing in Anopheles mosquitoes and humans. Reactive oxygen and nitrogen species threatening the parasite are either endogenously produced by heme derived from hemoglobin degradation or they are from exogenous sources such as the host immune defense. In order to maintain the intracellular redox balance, P. falciparum employs a complex thioredoxin and glutathione system based on the thioredoxin reductase/thioredoxin and glutathione reductase/glutathione couples. P. falciparum thioredoxin reductase reduces thioredoxin and a range of low molecular weight compounds, while glutathione reductase is highly specific for its substrate glutathione disulfide. Since Plasmodium spp. lack catalase and a classical glutathione peroxidase, their redox balance depends on a complex set of five peroxiredoxins differentially located in the cytosol, apicoplast, mitochondria, and nucleus with partially overlapping substrate preferences. Moreover, P. falciparum employs a set of members belonging to the thioredoxin superfamily such as three thioredoxins, two thioredoxin-like proteins, a dithiol and three monocysteine glutaredoxins, and a redox-active plasmoredoxin with largely redundant functions. This review aims at summarizing our current knowledge on the functional redox networks of the malaria parasite P. falciparum.
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