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

  • Kapishnikov S Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, 12489, Berlin, Germany. sergey.kapishnikov@nbi.ku.dk.
  • Grolimund D Paul Scherrer Institute, 5232, Villigen, PSI, Switzerland.
  • Schneider G Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, 12489, Berlin, Germany.
  • Pereiro E ALBA Synchrotron Light Source, MISTRAL Beamline-Experiments Division, 08290, Cerdanyola del Valles, Barcelona, Spain.
  • McNally JG Soft Matter and Functional Materials, Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15, 12489, Berlin, Germany. james.mcnally@helmholtz-berlin.de.
  • Als-Nielsen J Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark. jens.als.nielsen@gmail.com.
  • Leiserowitz L Department of Materials and Interfaces, Weizmann Institute of Science, Rehovot, 76100, Israel.
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  • 2017-08-10
Published in:
  • Scientific reports. - 2017
Cells, Cultured
Crystallization
Erythrocytes
Heme
Hemeproteins
Hemoglobins
Humans
Iron
Kinetics
Microscopy
Models, Chemical
Plasmodium falciparum
Spectrometry, X-Ray Emission
Vacuoles
X-Ray Microtomography
English 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.
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  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/13542
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