Recent advances in glycosome biogenesis and its implications for drug discovery

The phylum Euglenozoa, within the Eukaryote domain, includes diverse protists such as the medically significant kinetoplastids, characterized by their unique kinetoplast DNA. Both kinetoplastids and their sister class Diplonemea possess glycosomes – specialized microbodies that compartmentalize glycolysis and other metabolic pathways. Glycosomes likely evolved in a common ancestor of kinetoplastid and diplonemids, conferring metabolic flexibility and reducing cellular toxicity. These organelles are essential for parasite survival and thus, represent promising drug targets for treating kinetoplastid diseases. While the basic principles of peroxisome and glycosome biogenesis are conserved, distinct features in glycosome biogenesis machinery and a lower level of sequence conservation enables pathogen specific drug design for developing new therapies. This review summarizes our current knowledge on glycosome biogenesis, recent advances, and therapeutic potential for treating trypanosomatid infections.