The peculiarities and paradoxes of Plasmodium heme metabolism

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 va...

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Bibliographic Details
Published in:Annual review of microbiology 2014-01, Vol.68 (1), p.259-278
Main Authors: Sigala, Paul A, Goldberg, Daniel E
Format: Article
Language:English
Subjects:
Animals
Biosynthesis
Chemical compounds
Cytotoxicity
Heme - metabolism
Humans
Malaria
Malaria - metabolism
Malaria - parasitology
Metabolism
Parasites
Plasmodium
Plasmodium - metabolism
Vector-borne diseases
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Summary: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.
ISSN:0066-4227
1545-3251
DOI:10.1146/annurev-micro-091313-103537