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The causative agent of malaria, Plasmodium, possesses three translationally active compartments: the cytosol, the mitochondrion and a relic plastid called the apicoplast. Aminoacyl-tRNA synthetases to charge tRNA are thus required for all three compartments. However, the Plasmodiumfalciparum genome encodes too few tRNA synthetases to supply a unique enzyme for each amino acid in all three compartments. We have investigated the subcellular localisation of three tRNA synthetases (AlaRS, GlyRS and ThrRS), which occur only once in the nuclear genome, and we show that each of these enzymes is dually localised to the P. falciparum cytosol and the apicoplast. No mitochondrial fraction is apparent for these three enzymes, which suggests that the Plasmodium mitochondrion lacks at least these three tRNA synthetases. The unique Plasmodium ThrRS is the presumed target of the antimalarial compound borrelidin. Borrelidin kills P. falciparum parasites quickly without the delayed death effect typical of apicoplast translation inhibitors and without an observable effect on apicoplast morphology. By contrast, mupirocin, an inhibitor of the apicoplast IleRS, kills with a delayed death effect that inhibits apicoplast growth and division. Because inhibition of dual targeted tRNA synthetases should arrest translation in all compartments of the parasite, these enzymes deserve further investigation as potential targets for antimalarial drug development., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

The protein translation machinery of the parasite Plasmodium is the target of important anti-malarial drugs, and encompasses many promising targets for future drugs. Plasmodium parasites have three subcellular compartments that house genomes; the nucleus, mitochondrion and apicoplast, and each requires its own compartmentalized transcription and translation apparatus for survival. Despite the availability of the complete genome sequence that should reveal the requisite elements for all three compartments, our understanding of the translation machineries is patchy. We review what is known about cytosolic and organellar translation in Plasmodium and discuss the molecules that have been identified through genome sequencing and post-genomic analysis. Some translation components are yet to be found in Plasmodium, whereas others appear to be shared between translationally active organelles., (Copyright © 2011 Elsevier Ltd. All rights reserved.)