Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography

Abstract A key drug target for malaria has been the detoxification pathway of the iron-containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report...

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Auteurs principaux:	Sergey Kapishnikov, Daniel Grolimund, Gerd Schneider, Eva Pereiro, James G. McNally, Jens Als-Nielsen, Leslie Leiserowitz
Format:	article
Langue:	EN
Publié:	Nature Portfolio 2017
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/0985f7d76d7140ed84de25c8f8e8ac97
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spelling	oai:doaj.org-article:0985f7d76d7140ed84de25c8f8e8ac972021-12-02T15:05:04ZUnraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography10.1038/s41598-017-06650-w2045-2322https://doaj.org/article/0985f7d76d7140ed84de25c8f8e8ac972017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06650-whttps://doaj.org/toc/2045-2322Abstract A key drug target for malaria has been the detoxification pathway of the iron-containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report new results of in vivo rate of heme crystallization in the malaria parasite, based on a new technique to measure element-specific concentrations at defined locations in cell ultrastructure. Specifically, a high resolution correlative combination of cryo soft X-ray tomography has been developed to obtain 3D parasite ultrastructure with cryo X-ray fluorescence microscopy to measure heme concentrations. Our results are consistent with a model for crystallization via the heme detoxification protein. Our measurements also demonstrate the presence of considerable amounts of non-crystalline heme in the digestive vacuole, which we show is most likely contained in hemoglobin. These results suggest a tight coupling between hemoglobin digestion and heme crystallization, highlighting a new link in the crystallization pathway for drug development.Sergey KapishnikovDaniel GrolimundGerd SchneiderEva PereiroJames G. McNallyJens Als-NielsenLeslie LeiserowitzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sergey Kapishnikov Daniel Grolimund Gerd Schneider Eva Pereiro James G. McNally Jens Als-Nielsen Leslie Leiserowitz Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
description	Abstract A key drug target for malaria has been the detoxification pathway of the iron-containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report new results of in vivo rate of heme crystallization in the malaria parasite, based on a new technique to measure element-specific concentrations at defined locations in cell ultrastructure. Specifically, a high resolution correlative combination of cryo soft X-ray tomography has been developed to obtain 3D parasite ultrastructure with cryo X-ray fluorescence microscopy to measure heme concentrations. Our results are consistent with a model for crystallization via the heme detoxification protein. Our measurements also demonstrate the presence of considerable amounts of non-crystalline heme in the digestive vacuole, which we show is most likely contained in hemoglobin. These results suggest a tight coupling between hemoglobin digestion and heme crystallization, highlighting a new link in the crystallization pathway for drug development.
format	article
author	Sergey Kapishnikov Daniel Grolimund Gerd Schneider Eva Pereiro James G. McNally Jens Als-Nielsen Leslie Leiserowitz
author_facet	Sergey Kapishnikov Daniel Grolimund Gerd Schneider Eva Pereiro James G. McNally Jens Als-Nielsen Leslie Leiserowitz
author_sort	Sergey Kapishnikov
title	Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
title_short	Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
title_full	Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
title_fullStr	Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
title_full_unstemmed	Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
title_sort	unraveling heme detoxification in the malaria parasite by in situ correlative x-ray fluorescence microscopy and soft x-ray tomography
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0985f7d76d7140ed84de25c8f8e8ac97
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Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography

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