Glycosome biogenesis in trypanosomes and the de novo dilemma

Abstract

Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell. Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis and matrix protein import, have been identified in T. brucei. Based on these findings, it is widely accepted that glycosomes proliferate through growth and division of existing organelles; however, to our knowledge, a de novo mechanism of biogenesis has not been directly demonstrated. Here, we review recent findings that provide support for the existence of an endoplasmic reticulum (ER)-derived de novo pathway of glycosome biogenesis in T. brucei. Two studies recently identified PEX13.1, a peroxin involved in matrix protein import, in the ER of procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been found in the ER of cells undergoing de novo biogenesis of peroxisomes. In addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are important for de novo biogenesis in other eukaryotes. Because glycosomes are rapidly remodeled via autophagy during life cycle differentiation, de novo biogenesis could provide a method of restoring glycosome populations following turnover. Together, the findings we summarize provide support for the hypothesis that glycosome proliferation occurs through growth and division of pre-existing organelles and de novo biogenesis of new organelles from the ER and that the level each mechanism contributes is influenced by glucose availability.

Structure, Properties, and Function of Glycosomes in Trypanosoma cruzi

“…Glycosome biogenesis has been studied in detail in T. brucei and to a lesser extent in Leishmania spp. (reviewed in Galland and Michels, 2010;Gualdrón-López et al, 2013;Haanstra et al, 2016;Bauer and Morris, 2017). However, few studies have been devoted to this process in T. cruzi.…”

Fusarium verticillioides FvPex8 is a key component of peroxisomal docking/translocation module that serves important roles in fumonisin biosynthesis but not in virulence

“…Plant glyoxysomes play essential roles in glyoxylate cycle, embryonic development, and gametophytic function (Hu et al, 2012, Boisson-Dernier et al, 2008. Glycosomes in Trypanosomes perform important glycolytic reactions (Bauer & Morris, 2017). In filamentous fungi, a specific type of peroxisome known as Woronin bodies are associated with septal pore maintenance and cellular integrity (Jedd & Chua, 2000).…”

Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation

“…In addition to the conventional organelles typical of eukaryotic cells, evolutionarily divergent kinetoplastid parasites are characterised by their possession of glycosomes, specialist organelles that harbour the enzymes of glycolysis (3). Although unique in their compartmentation of glycolytic enzymes, glycosomes are related to peroxisomes, sharing with those organelles a similar (though divergent) machinery for import, insertion of membrane proteins (PEX16, PEX19) and peroxisome proliferation, as well as their capacity for either lipid, purine and pyrimidine biosynthesis (4). Glycosomes are also dynamic in composition and number in response to the metabolic demands of the parasite, their synthesis and turnover involving similar biogenesis and degradation mechanisms to those of the peroxisomes of yeast and mammalian cells.…”