The Plasmodium heme detoxification protein functions in mitochondrial protein synthesis.

Authors

Louis Sarrazin, Melissa R Rosenthal, Joachim Kloehn, Tanja Ziesmann, Yasmin Schmitz, Anna-Lena Sandtmann, Robert Domènech-Eres, Katharina Scholz-Höhn, Coralie Boulet, Ute Distler, Daniel E Goldberg, Joachim M Matz

Published in

Nature communications. Volume 17. Issue 1. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Malaria blood-stage parasites digest ~80% of host cell hemoglobin within a degradative vacuole, releasing heme that is detoxified by sequestration into hemozoin crystals. Although essential for survival and a validated drug target, the mechanisms of heme biomineralization remain unclear. Here, we study the parasite's Heme Detoxification Protein (HDP), previously proposed to mediate hemozoin formation, using genetic, microscopic, bioenergetic, and proteomic approaches. Endogenous tagging reveals that HDP localizes to the mitochondrion, not the digestive vacuole. HDP inactivation has no effect on heme biomineralization, but causes mitochondrial depolarization, proguanil hypersensitivity, and developmental arrest, which is rescued by bypassing respiratory-chain-dependent pyrimidine biosynthesis. HDP knockout abolishes mitochondrial electron flow due to loss of complexes III and IV, consistent with impaired mitochondrial protein synthesis. Integration of structural modelling with quantitative proteomics places HDP within the mitoribosomal large subunit. Here, we show that HDP is essential for mitochondrial function and does not contribute to hemozoin formation.

PMID:
42567866
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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