Trypanosoma brucei aquaglyceroporins mediate the transport of metabolic end-products: Methylglyoxal, D-lactate, L-lactate and acetate.

Bloodstream forms of Trypanosoma (T.) brucei, the causative agent of African sleeping sickness, possess a highly active glycolysis, which generates as main end-products: pyruvate under aerobic conditions, and pyruvate and glycerol under anaerobic conditions. To secrete them into the extracellular milieu, the parasites have at least two main specific membrane proteins, the pyruvate transporter and the aquaglyceroporins However, there are several other minor products from the glycolysis that must be excreted by the parasites and whose exit pathway until now remained elusive. As aquaglyceroporins from T. brucei (TbAQP1, 2, and 3) show a wide permeability profile for small solutes, we decided to evaluate if these proteins allow the passage of methylglyoxal, L-lactate, D-lactate and acetate molecules. We expressed heterologously TbAQP1, 2, and 3 in aquaglyceroporin-null yeast cells or in Xenopus laevis oocytes and demonstrated that these channels are permeable for methylglyoxal, L-lactate, D-lactate and acetate. We further demonstrate that methylglyoxal is highly toxic for bloodstream forms of T. brucei, while L-lactate and D-lactate appear almost harmless. Additionally, we discuss all our findings in the light of the novel metabolic discoveries, putting in context the participation of TbAQP1, 2, 3, and other proteins in the excretion of unwanted metabolic end-products.