Compartmentation of Redox Metabolism in Malaria Parasites

PLoS Pathogens

Jude M. Przyborski¹  Stefan Rahlfs²  Katja Becker²  Sebastian Kehr²  Nicole Sturm² 

[1] Department of Parasitology, Faculty of Biology, Philipps University Marburg, Marburg, Germany;Interdisciplinary Research Centre, Justus Liebig University, Giessen, Germany

关键词: Plasmodium;    Malarial parasites;    Mitochondria;    Parasitic diseases;    Cytosol;    Oxidation-reduction reactions;    Signal peptides;    Parasitophorous vacuole;   

DOI  :  10.1371/journal.ppat.1001242

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito – a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes – glutathione reductase and thioredoxin reductase – Plasmodium makes use of alternative-translation-initiation (ATI) to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention.

【 授权许可】

CC BY