Autophagy in Trypanosomatids

Abstract

Autophagy is a ubiquitous eukaryotic process that also occurs in trypanosomatid parasites, protist organisms belonging to the supergroup Excavata, distinct from the supergroup Opistokontha that includes mammals and fungi. Half of the known yeast and mammalian AuTophaGy (ATG) proteins were detected in trypanosomatids, although with low sequence conservation. Trypanosomatids such as Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for serious tropical diseases in humans. The parasites are transmitted by insects and, consequently, have a complicated life cycle during which they undergo dramatic morphological and metabolic transformations to adapt to the different environments. Autophagy plays a major role during these transformations. Since inhibition of autophagy affects the transformation, survival and/or virulence of the parasites, the ATGs offer promise for development of drugs against tropical diseases. Furthermore, various trypanocidal drugs have been shown to trigger autophagy-like processes in the parasites. It is inferred that autophagy is used by the parasites in an—not always successful—attempt to cope with the stress caused by the toxic compounds.

Tim62, a Novel Mitochondrial Protein in Trypanosoma brucei, Is Essential for Assembly and Stability of the TbTim17 Protein Complex

“…These diseases are spread by insect vectors and affect millions of people worldwide. Trypanosomatids are unicellular parasitic protozoa that belong to the eukaryotic super group excavata (4,5). These organisms are also classified as the early branching eukaryotes, which possess a single mitochondrion with a large concatenated structure of mitochondrial DNA, known as kinetoplast or kDNA (6 -8).…”

Starvation-response may not involve Atg1-dependent autophagy induction in non-unikont parasites

“…However, there is difference between fungi and human or fungi and Arabidopsis in case of proteins important for specific autophagy-related processes32. Several comprehensive bioinformatics studies were carried out on protozoan genomes, and discussed the presence of ATG genes and the differences in presence among species58333435. Lack of some ATG genes were demonstrated220, including the Atg12 ubiquitin-like conjugation system25634 or Atg172.…”

“…Several comprehensive bioinformatics studies were carried out on protozoan genomes, and discussed the presence of ATG genes and the differences in presence among species58333435. Lack of some ATG genes were demonstrated220, including the Atg12 ubiquitin-like conjugation system25634 or Atg172. Remarkably, many of these studies showed the presence of ATG1 gene in non-unikont parasites23419.…”

Between Armour and Weapons — Cell Death Mechanisms in Trypanosomatid Parasites

“…Starved epimastigotes express Atg8.1, but such expression is decreased in metacyclic forms [82,92]. Reservosomes disappeared during differentiation, most likely due to the cysteine proteinase activity, in particular, cruzipain [159,191,192].…”

“…In the sandfly, the exposure of promastigotes to different stress stimuli, including higher temperature, low pH, and nutritional deprivation, acts as a crucial event for the success of the metacyclogenesis [189,192]. L. mexicana shows that lysosome-like structures, called megasomes, are involved in parasite differentiation, with the activity of two megasomal cysteine peptidases (CPA and CPB) associated with autophagy.…”