The peculiarities and paradoxes of Plasmodium heme metabolism

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


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.

Keywords: biosynthesis; hemozoin; malaria; porphyrins; trafficking.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Heme / metabolism*
  • Humans
  • Malaria / metabolism
  • Malaria / parasitology*
  • Plasmodium / metabolism*


  • Heme