Metabolic functions of glycosomes in trypanosomatids

Abstract

Protozoan Kinetoplastida, including the pathogenic trypanosomatids of the genera Trypanosoma and Leishmania, compartmentalize several important metabolic systems in their peroxisomes which are designated glycosomes. The enzymatic content of these organelles may vary considerably during the life-cycle of most trypanosomatid parasites which often are transmitted between their mammalian hosts by insects. The glycosomes of the Trypanosoma brucei form living in the mammalian bloodstream display the highest level of specialization; 90% of their protein content is made up of glycolytic enzymes. The compartmentation of glycolysis in these organelles appears essential for the regulation of this process and enables the cells to overcome short periods of anaerobiosis. Glycosomes of all other trypanosomatid forms studied contain an extended glycolytic pathway catalyzing the aerobic fermentation of glucose to succinate. In addition, these organelles contain enzymes for several other processes such as the pentose-phosphate pathway, beta-oxidation of fatty acids, purine salvage, and biosynthetic pathways for pyrimidines, ether-lipids and squalenes. The enzymatic content of glycosomes is rapidly changed during differentiation of mammalian bloodstream-form trypanosomes to the forms living in the insect midgut. Autophagy appears to play an important role in trypanosomatid differentiation, and several lines of evidence indicate that it is then also involved in the degradation of old glycosomes, while a population of new organelles containing different enzymes is synthesized. The compartmentation of environment-sensitive parts of the metabolic network within glycosomes would, through this way of organelle renewal, enable the parasites to adapt rapidly and efficiently to the new conditions.

Glycosome turnover inLeishmania majoris mediated by autophagy

“…These include the glycosomes, peroxisome-related microbodies that contain enzymes of several important metabolic pathways including glycolysis, the pentose-phosphate pathway, b-oxidation of fatty acids, gluconeogenesis, purine salvage, and biosynthesis of pyrimidines, ether lipids and squalenes. 23 Compartmentalization of metabolic pathways in this manner prevents the accumulation of toxic intermediates which would otherwise damage the cell, 24 and is also thought to facilitate rapid metabolic adaptation in response to changing environments. 23 Studies in both Leishmania and trypanosomes have shown that proper biogenesis of glycosomes and the correct targeting of glycosomal enzymes are essential for parasite survival, [24][25][26][27][28][29] making these unique organelles an attractive drug target.…”

Exploiting death: apoptotic immunity in microbial pathogenesis

“…The subcellular compartmentalization of glycolysis in trypanosomatids is fundamentally different than in all other eukaryotes, where glycolysis ensues cytoplasmically. In trypanosomatids, the majority of glycolytic enzymes are contained in unusual peroxisome-like organelles termed 'glycosomes'; only the terminal three glycolytic enzymes are cytosolic 48,49 (see Figure 3). Thus in trypanosomatids, GAPDH and enolase exist in distinct intracellular locales and are unassociated.…”

“…This 'reversed' behavior was attributable genetically to E1B 19 K. That authentic Bcl-2 could substitute for E1B 19 K, but that it does not program such a reversed behavior in the context of Figure 3 Glycosomal localization of glycolytic enzymes. Enzymes and intermediates of glycolysis that are found within and without the glycosome 48,49 are diagrammed here. Glycosomes are intracellular peroxisome-like organelles of trypanosomatids, constrained by a single lipid bilayer membrane (represented by a double solid line), within which the proximal steps of glycolysis ensue.…”

“…Glycosomal contents vary during the heteroxenous trypanosomatid life cycle, and other metabolic processes (including glycerol catabolism) also are localized within. 49 Intraglycosomal glycolytic enzymes are shown as darker (purple) boxes; extraglycosomal (cytosolic) glycolytic enzymes are shown as lighter (blue) boxes. Filled boxes denote those glycolytic enzymes whose mammalian homologs are externalized on the apoptotic cell surface (see Figure 1) uninfected mammalian cells suggests the additional contribution of other adenoviral gene(s).…”

Caracterização molecular e funcional da imidazolona propionase de <i>Trypanosoma cruzi</i>: uma enzima do metabolismo de histidina.

“…Além disso, enzimas relacionadas a outras vias, como β-oxidação de ácidos graxos, recrutamento de purinas e vias biossintéticas para pirimidinas podem estar presentes nos glicossomos (Michels et al, 2006). Outras organelas encontradas no citoplasma de T. cruzi são os reservossomos e os acidocalcisomas.…”