Cited by 131Malaria Research and ControlErythrocyte Function and PathophysiologyHemoglobin structure and function

The Peculiarities and Paradoxes of Plasmodium Heme Metabolism

Sigala, Paul A., Goldberg, Daniel E.·2014·Annual Review of Microbiology

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.

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Crossref · 10.1146/annurev-micro-091313-103537

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137 of 137 references verified0 citation errors · 0 not checkable

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  • Anti-malarial drugs target Plasmodium heme metabolism in most cases.

    “Perhaps the strongest argument in support of this strategy is provided by anti-malarial drugs, which target in most cases Plasmodium heme metabolism [239].”

    From The Iron age of host–microbe interactions (2015) · cites this paper as [239]

  • Plasmodium spp. invade and multiply inside red blood cells and access their heme-iron content.

    “Perhaps the clearest example of such a strategy is the one co-opted by Plasmodium spp., which invade and proliferate inside RBC, accessing their heme-Fe content (71).”

    From Innate Nutritional Immunity (2018) · cites this paper as [71]

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Authors
Sigala, P. A., & Goldberg, D. E.
Affiliations
Howard Hughes Medical Institute (US)
Venue
Annual Review of Microbiology
Published
2014-09-08
Volume
68
Issue
1
Pages
259-278
ISSN
  • 0066-4227 (ISSN-L)
  • 1545-3251
OpenAlex
W2158967285
Cited by
129
References
138
Citations by year
2026: 11 · 2025: 12 · 2024: 9 · 2023: 4 · 2022: 13 · 2021: 8 · 2020: 16 · 2019: 10 · 2018: 10 · 2017: 19 · 2016: 9 · 2015: 7 · 2014: 1
FWCI
1.89
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
Plasmodium, heme metabolism, heme biosynthesis, hemozoin, malaria, digestive vacuole, hemoglobin degradation, electron transport, antimalarial drug targets
MeSH terms
Animals, Heme, Humans, Malaria, Plasmodium

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