Turnover of glycosomes in trypanosomes-perspectives for drug discovery

Ana Brennand, Eva Rico, Melisa Gualdrón-López, Paul A.M. Michels

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

A unique feature of trypanosomatids is the compartmentalization of the majority of the enzymes of glycolysis and gluconeogenesis, as well as several other important metabolic processes within peroxisome-related organelles designated as glycosomes. Considerable variations can be observed between the enzyme content of glycosomes from different developmental forms of trypanosomatids. These differences reflect how the parasites adapt the metabolic repertoire of the organelles to the distinct environments encountered during the successive stages of their life cycle. Several glycosomal pathways have been validated as drug targets, and drug discovery exploiting the unique properties of their enzymes is actively being pursued. But the correct sequestering of the enzymes inside glycosomes and the life-cycle-dependent tuning of the organelles' enzyme content are also crucial, rendering proteins involved in glycosome turnover - biogenesis and degradation - additional potential drug targets. In this chapter, we discuss the current knowledge about the proteins and mechanisms involved in the assembly and degradation of glycosomes, highlighting their differences with peroxisomes in the host cells. We assess the potential for development of compounds that selectively inhibit glycosome turnover in the parasites and could lead to development of new drugs against trypanosomatid-borne diseases.

Original languageEnglish
Title of host publicationA Comprehensive Analysis of Parasite Biology
Subtitle of host publicationFrom Metabolism to Drug Discovery
EditorsMüller Sylke, Cerdan Rachel, Radulescu Ovidiu
Place of PublicationWeinheim, Germany
PublisherWiley-VCH Verlag
Pages231-253
Number of pages23
ISBN (Electronic)9783527694082
ISBN (Print)9783527339044
DOIs
Publication statusPublished - 5 Aug 2016

Publication series

NameDrug Discovery in Infectious Diseases
PublisherWiley-VCH Verlag GmbH & Co. KGaA
Volume7

Keywords

  • drug discovery
  • gluconeogenesis
  • glycolysis
  • glycosomes
  • peroxisomal membrane proteins
  • trypanosomatid-borne diseases

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