PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum.
The human malaria parasite Plasmodium falciparum is capable of adapting to vastly different extracellular Ca(2+) environments while maintaining tight control of its intracellular Ca(2+) concentration. The mechanisms underpinning Ca(2+) homeostasis in this important pathogen are only partly understood. Here we have functionally expressed the putative Ca(2+)/H(+) antiporter PfCHA in Xenopus laevis oocytes. Our data suggest that PfCHA mediates H(+)-coupled Ca(2+) and Mn(2+) exchange. The apparent dissociation constant K(M) for Ca(2+) of 2.2 +/- 0.7 mM and the maximal velocity V(max) of 0.6 +/- 0.1 nmol per oocyte per hour are consistent with PfCHA being a low-affinity high-capacity Ca(2+) 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 Ca(2+) dynamics, suggest that the mitochondrion serves as a dynamic Ca(2+) store and that PfCHA functions as a Ca(2+) efflux system expelling excess Ca(2+) from the mitochondrion. PfCHA lacks appreciable homologies to the human mitochondrial Ca(2+)/H(+) exchanger and might represent an evolutionary divergent class of mitochondrial cation antiporter, which, in turn, might provide novel opportunities for intervention.
Rotmann
Alexander
A
Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
Sanchez
Cecilia
C
Guiguemde
Armand
A
Rohrbach
Petra
P
Dave
Anurag
A
Bakouh
Naziha
N
Planelles
Gabrielle
G
Lanzer
Michael
M
D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism*; D015870:Gene Expression; D007700:Kinetics; D008345:Manganese / Q000378:metabolism; D008928:Mitochondria / Q000737:chemistry; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D009865:Oocytes; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011522:Protons; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D017920:Antiporters; D002413:Cations, Divalent; D024101:Mitochondrial Proteins; D011522:Protons; D015800:Protozoan Proteins; D008345:Manganese; D002118:Calcium