Hemozoin: a Complex Molecule with Complex Activities.

Abstract

Malaria is a disease caused by parasites that reside in host red blood cells and use hemoglobin as a nutrient source. Heme released by hemoglobin catabolism is modified by the parasite to produce hemozoin (HZ), which has toxic effects on the host. Experimentation aiming to elucidate how HZ contributes to malaria pathogenesis has utilized different preparations of this molecule, complicating interpretation and comparison of findings. We examine natural synthesis and isolation of HZ and highlight studies that have used multiple preparations, including synthetic forms, in a comparative fashion. Recent work utilizing sophisticated imaging and detection techniques reveals important molecular characteristics of HZ synthesis and biochemistry. Other recent studies further refine understanding of contributions of HZ to malaria pathogenesis yet highlight the continuing need to characterize HZ preparations and contextualize experimental conditions in the in vivo infection milieu. This review highlights the necessity of collectively determining what is physiologically relevant HZ. Characterization of isolated natural HZ and use of multiple preparations in each study are recommended with application of in vivo studies whenever possible. Adoption of such practices is expected to improve reproducibility of results and elucidate the myriad of ways that HZ participates in malaria pathogenesis.