Autophagy and Related processes in Trypanosomatids: Insights from Genomic and Bioinformatic Analyses

The autophagic pathway is a key component in the lysosomal dependent entry ofTrypanosoma cruziinto the host cell

“…38 Moreover, as we have mentioned above, rapamycin is a specific Tor kinase inhibitor; the presence of this kinase in trypanosomatids was predicted in the genome data base. 49,50 Here, for the first time, we demonstrated the presence of the Tor kinase in T. cruzi at a functional level by using a compound that specifically inhibits its enzymatic action. Therefore, our results are in agreement with a recently published work showing that incubation of epimastigotes (E) with PBS during 18 h increases the in vitro differentiation to metacyclic trypomastigotes (MT) and that a high expression of the Atg8 protein is observed in the intermediate forms between E and MT.…”

Autophagy in protists

“…Genome database searches supplemented with more advanced analyses have revealed that only half of the autophagy-associated components characterized in S. cerevisiae are present in trypanosomatids. 14,15,17,18,20 However, comparisons with other organisms show less dramatic differences since data suggest that a number of autophagy-related proteins e.g., Atg19, Atg21, Atg22, Atg23, Atg25, Atg28, Atg29, Atg30 and Cis1/Atg31 arose as innovations in the fungal lineage: There is no good evidence that they have orthologues outside fungi. 6,14 Nevertheless, it remains likely that further lineage-specific innovations, as well as expansions outlined elsewhere, remain to be discovered.…”

“…For example, it has been initially suggested that the second Atg12-based conjugation system was absent in trypanosomatids. 18 However, later reports 14,15,23 identify Atg5 and Atg10 orthologues, recently experimentally characterized. 23 Interestingly, despite the identification…”

“…These predictions are significantly enhanced by the availability of structural data but, as yet, rather few autophagy proteins have been fully structurally characterized. 18 Many autophagy proteins contain multiple domains 18 and these can cause problems, especially in the case of short domains and large inter-domain separations. Since BLAST will separate out individual domain matches in such cases, two proteins may pass the orthology prediction test yet differ in their domain composition.…”

“…14,[16][17][18][19][20][21][22][23] For some of the species examined so far, genomic signatures are complemented by experimental demonstrations of autophagy and/or analyses of candidate protein function. Significantly, however, bioinformatics surveys of protist genomes reveal some taxa in which autophagy, at least as defined by current paradigms, does not occur and others in which the canonical autophagy pathway has been subject to lineage-specific elaboration or moderation.…”