Autophagy and related processes in trypanosomatids: insights from genomic and bioinformatic analyses.

The targeting in eukaryotic cells of cellular components to the lysosome or vacuole for degradation is called autophagy. Not only cytoplasmic macromolecules and bulk cytoplasm are subject to this process; entire organelles such as peroxisomes can be degraded. Autophagy of peroxisomes is called pexophagy. Unpublished evidence suggests that the analogous processing of glycosomes in the protozoan kinetoplastids occurs. Taking advantage of the (near-) complete status of three trypanosomatid genomes, a census of components of autophagy and related processes has been undertaken in these organisms. Simple database searches were supplemented by more advanced analyses where necessary. At most, only half of the components characterized in yeasts are present in trypanosomatids suggesting an unexpectedly streamlined version of autophagy occurs in these organisms. The cytoplasm-to-vacuole targeting (Cvt) system for delivery of proteins to the vacuole seems entirely absent in trypanosomatids. The accuracy of the census is supported by the coordinated absence of functionally linked components such as the conjugation system involving ATG12, ATG5, ATG10 and ATG16 that acts at the step of vesicle expansion and completion. Overall, the results are consistent with a scenario of taxon-specific addition of components to a minimal core, a hypothesis that should be readily testable by further genomic surveys allied to laboratory experiments. A bioinformatics analysis of the trypanosomatidal proteins was carried out, highlighting the paucity of information available regarding their structures and enabling prioritization of targets for future structural biology work.