Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target.
In trypanosomatids (Trypanosoma and Leishmania), protozoa responsible for serious diseases of mankind in tropical and subtropical countries, core carbohydrate metabolism including glycolysis is compartmentalized in peculiar peroxisomes called glycosomes. Proper biogenesis of these organelles and the correct sequestering of glycolytic enzymes are essential to these parasites. Biogenesis of glycosomes in trypanosomatids and that of peroxisomes in other eukaryotes, including the human host, occur via homologous processes involving proteins called peroxins, which exert their function through multiple, transient interactions with each other. Decreased expression of peroxins leads to death of trypanosomes. Peroxins show only a low level of sequence conservation. Therefore, it seems feasible to design compounds that will prevent interactions of proteins involved in biogenesis of trypanosomatid glycosomes without interfering with peroxisome formation in the human host cells. Such compounds would be suitable as lead drugs against trypanosomatid-borne diseases.
Moyersoen
Juliette
J
Research Unit for Tropical Diseases, Christian de Duve Institute of Cellular Pathology and Laboratory of Biochemistry, Université Catholique de Louvain, ICP-TROP 74.39, Avenue Hippocrate 74, B-1200 Brussels, Belgium.
Choe
Jungwoo
J
Fan
Erkang
E
Hol
Wim G J
WG
Michels
Paul A M
PA
D000818:Animals; D015195:Drug Design; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure; D008830:Microbodies / Q000187:drug effects* / Q000502:physiology; D008958:Models, Molecular; D020675:Peroxisomes / Q000187:drug effects / Q000502:physiology; D015800:Protozoan Proteins / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects* / Q000648:ultrastructure
D015800:Protozoan Proteins; D014344:Trypanocidal Agents