Abstract
The intraerythrocytic malaria parasite relies primarily on glycolysis to fuel its rapid growth and reproduction. The major byproduct of this metabolism, lactic acid, is extruded into the external medium. In this study, we show that the human malaria parasite Plasmodium falciparum expresses at its surface a member of the microbial formate-nitrite transporter family (PfFNT), which, when expressed in Xenopus laevis oocytes, transports both formate and lactate. The transport characteristics of PfFNT in oocytes (pH-dependence, inhibitor-sensitivity and kinetics) are similar to those of the transport of lactate and formate across the plasma membrane of mature asexual-stage P. falciparum trophozoites, consistent with PfFNT playing a major role in the efflux of lactate and hence in the energy metabolism of the intraerythrocytic parasite.
Highlights
The intraerythrocytic malaria parasite relies primarily on glycolysis to fuel its rapid growth and reproduction
Glucose is consumed by P. falciparum-infected erythrocytes at a rate some two orders of magnitude higher than by uninfected erythrocytes[2]
Glucose is metabolized via glycolysis to lactic acid, which is excreted in large quantities from the parasite[2] via a H þ -coupled transporter[7,8,9]
Summary
The intraerythrocytic malaria parasite relies primarily on glycolysis to fuel its rapid growth and reproduction. The protein encoded by PF3D7_0316600, referred to here as PfFNT (P. falciparum Formate–Nitrite Transporter), was, together with P. falciparum hexose transporter and the nucleoside/nucleobase transporter PfENT1, one of the very few (putative or proven) transporter proteins detected in a proteomic analysis of a detergent-resistant membrane fraction prepared from mature blood-stage P. falciparum parasites[13]. This is perhaps indicative of it playing an important housekeeping role in the intraerythrocytic phase of the malaria parasite’s life cycle. We have explored the function and subcellular localization of this protein, and here present data implicating it in the transport of lactic acid and other monocarboxylic acids across the plasma membrane of the intraerythrocytic parasite
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