Comparison of the peroxisomal matrix protein import system of different organisms. Exploration of possibilities for developing inhibitors of the import system of trypanosomatids for anti-parasite chemotherapy

Abstract

In recent decades, research on peroxisome biogenesis has been particularly boosted since the role of these organelles in metabolism became unraveled. Indeed in plants, yeasts and fungi, peroxisomes play an important role in the adaptation of metabolism during developmental processes and/or altered environmental conditions. In mammals their importance is illustrated by the fact that several severe human inherited diseases have been identified as peroxisome biogenesis disorders (PBD). Particularly interesting are the glycosomes – peroxisome-like organelles in trypanosomatids where the major part of the glycolytic pathway is sequestered – because it was demonstrated that proper compartmentalization of matrix proteins inside glycosomes is essential for the parasite.Although the overall process of peroxisome biogenesis seems well conserved between species, careful study of the literature reveals nonetheless many differences at various steps. In this review, we present a comparison of the first two steps of peroxisome biogenesis – receptor loading and docking at the peroxisomal membrane – in yeasts, mammals, plants and trypanosomatids and highlight major differences in the import process between species despite the conservation of (some of) the proteins involved.Some of the unique features of the process as it occurs in trypanosomatids will be discussed with regard to the possibilities for exploiting them for the development of compounds that could specifically disturb interactions between trypanosomatid peroxins. This strategy could eventually lead to the discovery of drugs against the diseases caused by these parasites.