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.
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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
- Publisher
- Annual Reviews
- 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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