Figure 8.

Proposed model for Thg action within P. falciparum. CPA and Thg are both able to release Ca²⁺ from the ER by inhibiting the P. falciparum SERCA (PfATP6). The presence of a Thg-Ca²⁺ response, even after emptying the ER with CPA, suggests that: (i) the two drugs target two intracellular Ca²⁺ pools, one sensitive to both SERCA inhibitors and one sensitive only to Thg; and (ii) alternatively the same Ca²⁺ pool could express two SERCA isoforms, one sensitive to both drugs and one sensitive only to Thg. If the latter is the case, the additional compartment was shown not to be the parasite mitochondrion or acidic pool. This additional compartment is crucial for SOCE in P. falciparum, because only Thg was able to activate Ca²⁺ influx into the parasite cytosol. PM, parasite plasma membrane; MT, mitochondrion; DV, digestive vacuole; CCI, constitutive Ca²⁺ influx; Hz, Hemozoin.