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Annu Rev Microbiol. 2014;68:259-78. doi: 10.1146/annurev-micro-091313-103537. Epub 2014 Jun 16.

The peculiarities and paradoxes of Plasmodium heme metabolism.

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Departments of Medicine and Molecular Microbiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110; email: ,


For over a century, heme metabolism has been recognized to play a central role during intraerythrocytic infection by Plasmodium parasites, the causative agent of malaria. Parasites liberate vast quantities of potentially cytotoxic heme as a by-product of hemoglobin catabolism within the digestive vacuole, where heme is predominantly sequestered as inert crystalline hemozoin. Plasmodium spp. also utilize heme as a metabolic cofactor. Despite access to abundant host-derived heme, parasites paradoxically maintain a biosynthetic pathway. This pathway has been assumed to produce the heme incorporated into mitochondrial cytochromes that support electron transport. In this review, we assess our current understanding of the love-hate relationship between Plasmodium parasites and heme, we discuss recent studies that clarify several long-standing riddles about heme production and utilization by parasites, and we consider remaining challenges and opportunities for understanding and targeting heme metabolism within parasites.


biosynthesis; hemozoin; malaria; porphyrins; trafficking

[Indexed for MEDLINE]

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