Biogenesis and metabolic homeostasis of trypanosomatid glycosomes: New insights and new questions

Abstract

Kinetoplastea and Diplonemea possess peroxisome‐related organelles that, uniquely, contain most of the enzymes of the glycolytic pathway and are hence called glycosomes. Enzymes of several other core metabolic pathways have also been located in glycosomes, in addition to some characteristic peroxisomal systems such as pathways of lipid metabolism. A considerable amount of research has been performed on glycosomes of trypanosomes since their discovery four decades ago. Not only the role of the glycosomal enzyme systems in the overall cell metabolism appeared to be unique, but also the organelles display remarkable features regarding their biogenesis and structural properties. These features are similar to those of the well‐studied peroxisomes of mammalian and plant cells and yeasts yet exhibit also differences reflecting the large evolutionary distance between these protists and the representatives of other major eukaryotic lineages. Despite all research performed, many questions remain about various properties and the biological roles of glycosomes and peroxisomes. Here, we review the current knowledge about glycosomes, often comparing it with information about peroxisomes. Furthermore, we highlight particularly many questions that remain about the biogenesis, and the heterogeneity in structure and content of these enigmatic organelles, and the properties of their boundary membrane.

Delineating transitions during the evolution of specialised peroxisomes: Glycosome formation in kinetoplastid and diplonemid protists

“…Indeed, minimal simplicity of C-terminal tripeptide or N-terminal nonapeptide motifs, often without absolute requirement for amino acid specificity in order to confer some degree of organelle targeting, is readily compatible with Martin’s view that metabolic pathways could easily be rerouted in organisms whenever inevitable minor mis-targeting of proteins provides a small selective advantage; protein mis-targeting happens often in eukaryotic cells ( Martin, 2010 ). Conversely, free passage of metabolites <400 Da across glycosomal membranes ( Quiñones et al, 2020 ; Michels and Gualdrón-López, 2022) suggests ‘hard-wiring’ organelle re-routed cytosolic pathways is not necessarily readily achieved, thereby explaining a sometimes patchwork conservation of PTS motifs observed in some euglenozoan enzymes, as indicated in Supplementary Tables S1 and S2 . In this work, we also dated divergence of trypanosomatid peroxins to an early point in euglenozoan evolution.…”

“…peroxisomes in methylotrophic yeasts, woronin bodies in filamentous fungi, glyoxysomes in plants, recently discovered anaerobic peroxisomes in anaerobic amoebae ( Le et al, 2020 ; Verner et al, 2021 ) – provide other avenues for further discussion and experimentation. Many outstanding questions about glycosomes have recently been discussed by Michels and Gualdrón-López (2022) . Additional questions that speak to the evolution of these organelles and could be addressed experimentally are listed in Table 1 .…”

“…But unless current information in the databases is incomplete or alternative targeting signals are present in orthologues, the cytosolic fumarase loop is expanded with one or two neighbouring enzymes in different species. We anticipate the carbon metabolism network would not be substantially affected by rerouting these enzymes because of the existence of pores in membranes of peroxisomes, including glycosomes, considered to allow passage of solutes (inorganic ions and metabolites) with a molecular mass up to approximately 400 Da ( Antonenkov and Hiltunen, 2012 ; Gualdrón-López et al, 2012b ; Quiñones et al, 2020 ; Chornyi et al, 2021 ; Michels and Gualdrón-López, 2022 . The permissiveness of solute passage through peroxisomal membranes is a second key criterion with which any hypothesis about the origin of glycosomes should be compatible.…”

“…Glycosome biogenesis occurs by a process similar to that of peroxisomes in mammalian, plant and yeast cells, involving conserved proteins called peroxins or PEX proteins. T. brucei peroxins acting in various aspects of biogenesis have been identified–and orthologues also in other trypanosomatids ( Supplementary Figures S5 ) (reviewed by Galland and Michels, 2010 ; Bauer and Morris, 2017 ; Kalel and Erdmann, 2018 ; Michels and Gualdrón-López, 2022 ).…”

The bloodstream form ofTrypanosoma bruceidisplays non-canonical gluconeogenesis

“…In trypanosomatids, both glycolytic and gluconeogenic enzymes are localised within specialized organelles called glycosomes. Glycosomes are highly adapted peroxisomes, and they share related PEX-dependent import machineries [20]. In trypanosomatids, these organelles also harbour parts of the pentose phosphate pathway (PPP), nucleotide metabolism, and other associated pathways.…”