title: The peculiarities and paradoxes of Plasmodium heme metabolism.
abstract: 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.
authors.affiliation: Departments of Medicine and Molecular Microbiology and the Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110; email: sigala@wustl.edu , dgoldberg@wustl.edu.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sigala
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology*; D010961:Plasmodium / Q000378:metabolism*
chemical_list: D006418:Heme
keywords: biosynthesis; hemozoin; malaria; porphyrins; trafficking