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.
Highlights
Like other kinetoplastids, Trypanosoma cruzi contains peroxisome-related organelles called glycosomes (Figures 1A–D)
Enzymes showed often a dual distribution over glycosomes and cytosol, either due to partial compartmentalization (e.g., Concepción et al, 1999) or represented by distinct isoenzymes (e.g., BarrosÁlvarez et al, 2014). This spatial organization of pathways implies that glycosomal metabolism is firmly embedded in the trypanosomatid’s overall metabolism and that many metabolites that serve as substrates or products of glycosomal metabolism have to cross the membrane to connect them to the cytosolic parts of the pathways or for their further metabolism in other pathways located in different cellular compartments such as cytosol or mitochondrion
Based on the situation in peroxisomes and some preliminary experiments with T. brucei glycosomes (Visser et al, 2007; Igoillo-Esteve et al, 2011; Antonenkov and Hiltunen, 2012; Gualdrón-López et al, 2012b), it was proposed that the ABC and Mitochondrial Carrier Family (MCF) transporters are involved in the import of large molecules like fatty-acids and cofactors (ATP, NAD+, etc.) into glycosomes, while smaller molecules, with an estimated Mr of approximately 400 Da, such as glycolytic intermediates and inorganic ions pass through pores (Gualdrón-López et al, 2013)
Summary
Citation for published version: Quiñones, W, Acosta, H, Silva Gonçalves, C, Motta, MC, Gualdrón-López, M & Michels, P 2020, 'Structure, properties, and function of glycosomes in trypanosoma cruzi', Frontiers in Cellular and Infection Microbiology, vol 10, no. 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, uniquely distributed over different compartments, are integrated and regulated.
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