Genomic and Proteomic Evidence for the Presence of a Peroxisome in the Apicomplexan Parasite Toxoplasma gondii and Other Coccidia

Abstract

Apicomplexans are successful parasites responsible for severe human diseases including malaria, toxoplasmosis, and cryptosporidiosis. For many years, it has been discussed whether these parasites are in possession of peroxisomes, highly variable eukaryotic organelles usually involved in fatty acid degradation and cellular detoxification. Conflicting experimental data has been published. With the age of genomics, ever more high quality apicomplexan genomes have become available, that now allow a new assessment of the dispute. Here, we provide bioinformatic evidence for the presence of peroxisomes in Toxoplasma gondii and other coccidians. For these organisms, we have identified a complete set of peroxins, probably responsible for peroxisome biogenesis, division, and protein import. Moreover, via a global screening for peroxisomal targeting signals, we were able to show that a complete set of fatty acid β-oxidation enzymes is equipped with either PTS1 or PTS2 sequences, most likely mediating transport of these factors to putative peroxisomes in all investigated Coccidia. Our results further imply a life cycle stage-specific presence of peroxisomes in T. gondii and suggest several independent losses of peroxisomes during the evolution of apicomplexan parasites.

Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii

“…With recent bioinformatic analyses demonstrating the presence of a suite of Pex proteins in the coccidian apicomplexans, but not in other subclasses [ 5 , 19 , 20 ], functional analyses are demanded. However, previous studies in Toxoplasma have proven to be controvertible.…”

“…The relative lack of structural evidence may be due to lifecycle-dependent expression, with the peroxins characterised by upregulation during the extracellular stages of the lifecycle, oocysts and sporozoites. Future studies should be directed here, rather than at the more tractable, intracellular, tachyzoite forms [ 20 ]. In addition, in all eukaryotic systems studied to date, a membrane-bound docking complex of Pex13 and Pex14 is required for peroxisomal protein import [ 7 , 8 ].…”

“…In addition, in all eukaryotic systems studied to date, a membrane-bound docking complex of Pex13 and Pex14 is required for peroxisomal protein import [ 7 , 8 ]. However, an obvious Pex13 is missing in the genome of Toxoplasma and related coccidian parasites [ 19 , 20 ]. Furthermore, the identity and presence of Pex14 in Toxoplasma is disputed [ 5 , 19 , 20 ].…”

“…However, an obvious Pex13 is missing in the genome of Toxoplasma and related coccidian parasites [ 19 , 20 ]. Furthermore, the identity and presence of Pex14 in Toxoplasma is disputed [ 5 , 19 , 20 ]. Therefore, the exact mode of Pex5-mediated protein import into peroxisomes in the coccidia is unclear and further bioinformatic and functional analyses are warranted.…”

“…Clearly, the nature and/or presence of peroxisomes in the Apicomplexa requires further analyses. However, bioinformatic studies have very recently provided evidence, by virtue of the presence of encoded Pex and PTS-bearing proteins, that Toxoplasma and related coccidia harbour peroxisomes [ 5 , 19 , 20 ]. Here, we have taken a functional biology approach to define the Toxoplasma Pex5 as a functional orthologue of the yeast, but not human, protein.…”