Structure, Properties, and Function of Glycosomes in Trypanosoma cruzi

Abstract

Glycosomes are peroxisome-related organelles that have been identified in kinetoplastids and diplonemids. The hallmark of glycosomes is their harboring of the majority of the glycolytic enzymes. Our biochemical studies and proteome analysis of Trypanosoma cruzi glycosomes have located, in addition to enzymes of the glycolytic pathway, enzymes of several other metabolic processes in the organelles. These analyses revealed many aspects in common with glycosomes from other trypanosomatids as well as features that seem specific for T. cruzi. Their enzyme content indicates that T. cruzi glycosomes are multifunctional organelles, involved in both several catabolic processes such as glycolysis and anabolic ones. Specifically discussed in this minireview are the cross-talk between glycosomal metabolism and metabolic processes occurring in other cell compartments, and the importance of metabolite translocation systems in the glycosomal membrane to enable the coordination between the spatially separated processes. Possible mechanisms for metabolite translocation across the membrane are suggested by proteins identified in the organelle's membrane-homologs of the ABC and MCF transporter families-and the presence of channels as inferred previously from the detection of channel-forming proteins in glycosomal membrane preparations from the related parasite T. brucei. Together, these data provide insight in the way in which different parts of T. cruzi metabolism, although uniquely distributed over different compartments, are integrated and regulated. Moreover, this information reveals opportunities for the development of drugs against Chagas disease caused by these parasites and for which currently no adequate treatment is available.

Transcriptional remodeling during metacyclogenesis in Trypanosoma cruzi I

“…Previous studies in T. brucei have shown a decrease in the glycolytic pathway glycosomes in the infective form of the parasite in the vector, allowing the parasite a rapid regulation of the metabolism in response to low glucose environments [13]. An increase in the number of down-regulated genes in MTs, the infective form of T. cruzi present in the vector, is consistent with these findings; however, the presence of genes coding for fumarate hydratase, class I and malate dehydrogenase up-regulated in MTs, both enzymes being involved in the glycolytic branch and active as a consequence of a decrease in pyruvate synthesis, which would possibly explain the down-regulation of pyruvate hydrogenase observed in MTs [25]. The activation of the glycolytic arm and its relationship with the decrease in pyruvate has already been previously documented in T. cruzi CDTs in response to the presence of a cell matrix, the results observed here could infer the presence of these regulatory processes in other stages of T. cruzi but future mechanistic studies must be conducted to fulfill this hypothesis [26].…”

Influence of N-Methylation and Conformation on Almiramide Anti-Leishmanial Activity

“…The molecular targets of almiramide C have been studied using a combination of photo-affinity and fluorescent probes in T. brucei, and suggested to include integral membrane proteins found in glycosomes (e.g., GIM5 and PEX11), which are specific to kinetoplastid parasites [26]. Responsible for the first seven steps of glycolysis, the glycosome is a peroxisome-related organelle essential for parasite survival in the bloodstream stage [41]. Notably, translocation across the glycosomal membrane implicates transporter and pore-forming proteins [42], which may differ contingent on species and be modified in resistant strains.…”

From purines to purinergic signalling: molecular functions and human diseases

“…For example, the metabolon of glycolysis, termed a glycosome, is a multi-enzyme structure containing a series of glycosomal enzymes including hexokinase (HK), phosphofructokinase (PFK), alanine transferase (ALT) and many others. 22 Similar metabolon also exists in the de novo purine synthesis pathway. Using fluorescence imaging technique, all six enzymes in the de novo pathway have been found to interact with each other to form a metabolon, defined as “purinosome”.…”