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.

中文翻译：

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通过原位相关X射线荧光显微镜和软X射线断层扫描揭示疟原虫中的血红素解毒作用。

疟疾的主要药物靶标是含铁分子血红素的排毒途径，这是血红蛋白消化的有毒副产物。血红素排毒的基石是其被螯合到血红蛋白晶体中，但是如何发生仍是不确定的。我们报告了一种新的技术，以测量在细胞超微结构中定义位置的元素特定浓度为基础的一种新技术，在疟疾寄生虫中血红素结晶的体内速率的新结果。具体而言，已经开发了冷冻软X射线断层扫描的高分辨率相关组合，以利用冷冻X射线荧光显微镜术测量血红素浓度来获得3D寄生虫超微结构。我们的结果与通过血红素解毒蛋白结晶的模型一致。我们的测量结果还表明，在消化液泡中存在大量的非结晶血红素，我们发现血红蛋白中极有可能含有非结晶血红素。这些结果表明血红蛋白消化和血红素结晶之间紧密结合，突显了药物开发结晶途径中的新联系。