The peculiarities and paradoxes of plasmodium heme metabolism

Paul A. Sigala, Daniel E. Goldberg

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

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.

Original languageEnglish
Pages (from-to)259-278
Number of pages20
JournalAnnual review of microbiology
Volume68
DOIs
StatePublished - Sep 8 2014

Keywords

  • Biosynthesis
  • Hemozoin
  • Malaria
  • Porphyrins
  • Trafficking

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