Summary
Artemisinin-based therapies are central to malaria treatment, but their efficacy is threatened by the emergence of resistant Plasmodium falciparum strains. While the role of Pfkelch13 mutations in clinical resistance is well established, recent reports from Africa implicate Pfcoronin mutations in treatment failure, adding to the complexity of resistance mechanisms. Here, we show that Pf Coronin, a non-essential actin regulator active during the ring-stage, facilitates efficient hemoglobin uptake. We demonstrate that resistance-associated Pfcoronin mutations disrupt Pf Coronin’s interaction with Pf Actin and its ring-stage localization, leading to impaired endocytosis and reduced hemoglobin acquisition. Pf Coronin and Pf Kelch13 function in distinct cellular regions; mutations in both converge to limit heme availability and artemisinin activation. Although Pf Coronin is dispensable for parasite viability, our findings demonstrate that Pfcoronin mutations reduce endocytosis and modulate artemisinin susceptibility during the clinically relevant ring stage—highlighting how non-essential, temporally restricted proteins can shape antimalarial drug response and resistance.
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