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

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The Peculiarities and Paradoxes of Plasmodium Heme Metabolism

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

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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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Authors: Sigala, P. A., & Goldberg, D. E.
Affiliations: Howard Hughes Medical Institute (US)
ORCID: Sigala, Paul A.
Goldberg, Daniel E.
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
DOI: 10.1146/annurev-micro-091313-103537
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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The Peculiarities and Paradoxes of Plasmodium Heme Metabolism

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