The DOI matches its Crossref record; 137 of the 138 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
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Pagola, S., Stephens, P. W., Bohle, D. S., Kosar, A. D., & Madsen, S. K. (2000) · Nature · doi:10.1038/35005132 · Cited by 862
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Phillips, M. A., Burrows, J. N., Manyando, C., van Huijsduijnen, R. H., Voorhis, W. C. V., & Wells, T. N. C. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.50 · Cited by 681
Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum
Wang, J., Zhang, C., Chia, W. N., Loh, C. S., Li, Z., Lee, Y. M., He, Y., Yuan, L., Lim, T. K., Liu, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms10111 · Cited by 649
Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic
Blasco, B., Leroy, D., & Fidock, D. A. (2017) · Nature Medicine · doi:10.1038/nm.4381 · Cited by 585
Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes
Bushell, E., Gomes, A. R., Sanderson, T., Anar, B., Girling, G., Herd, C., Metcalf, T., Modrzynska, K., Schwach, F., Martin, R. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.030 · Cited by 525
Haldar, K., Bhattacharjee, S., & Safeukui, I. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.161 · Cited by 454
Metadata
- 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 (medical) › Erythrocyte Function and Pathophysiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › 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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