PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum

• Verfasst von: Rotmann, Alexander [VerfasserIn]
• Verfasst von: Sanchez, Cecilia P. [VerfasserIn]
• Verfasst von: Guiguemde, Armand [VerfasserIn]
• Verfasst von: Rohrbach, Petra [VerfasserIn]
• Verfasst von: Dave, Anurag [VerfasserIn]
• Verfasst von: Bakouh, Naziha [VerfasserIn]
• Verfasst von: Planelles, Gabrielle [VerfasserIn]
• Verfasst von: Lanzer, Michael [VerfasserIn]
• Titel: PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum
• Verf.angabe: Alexander Rotmann, Cecilia Sanchez, Armand Guiguemde, Petra Rohrbach, Anurag Dave, Naziha Bakouh, Gabrielle Planelles and Michael Lanzer
• E-Jahr: 2010
• Jahr: 14 May 2010
• Umfang: 16 S.
• Fussnoten: Gesehen am 21.06.2023
• Titel Quelle: Enthalten in: Molecular microbiology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1987
• Jahr Quelle: 2010
• Band/Heft Quelle: 76(2010), 6 vom: Juni, Seite 1591-1606
• ISSN Quelle: 1365-2958
• DOI: doi:10.1111/j.1365-2958.2010.07187.x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1850753865

Abstract

The human malaria parasite Plasmodium falciparum is capable of adapting to vastly different extracellular Ca2+ environments while maintaining tight control of its intracellular Ca2+ concentration. The mechanisms underpinning Ca2+ homeostasis in this important pathogen are only partly understood. Here we have functionally expressed the putative Ca2+/H+ antiporter PfCHA in Xenopus laevis oocytes. Our data suggest that PfCHA mediates H+-coupled Ca2+ and Mn2+ exchange. The apparent dissociation constant KM for Ca2+ of 2.2 ± 0.7 mM and the maximal velocity Vmax of 0.6 ± 0.1 nmol per oocyte per hour are consistent with PfCHA being a low-affinity high-capacity Ca2+ carrier. In the parasite, PfCHA was found to localize to the mitochondrion. Physiological studies conducted with live parasitized erythrocytes, and using Fluo-4 and Rhod-2 to monitor cytoplasmic and mitochondrial Ca2+ dynamics, suggest that the mitochondrion serves as a dynamic Ca2+ store and that PfCHA functions as a Ca2+ efflux system expelling excess Ca2+ from the mitochondrion. PfCHA lacks appreciable homologies to the human mitochondrial Ca2+/H+ exchanger and might represent an evolutionary divergent class of mitochondrial cation antiporter, which, in turn, might provide novel opportunities for intervention.