Aronova Maria A, Noh Seung-Jae, Zhang Guofeng, Byrnes Colleen, Meier Emily Riehm, Kim Young C, Leapman Richard D
Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, USA.
Penta Medix Co., Ltd., Seongnam, Gyeonggi-do, Republic of Korea.
iScience. 2021 Jul 24;24(8):102901. doi: 10.1016/j.isci.2021.102901. eCollection 2021 Aug 20.
In the finely regulated process of mammalian erythropoiesis, the path of the labile iron pool into mitochondria for heme production is not well understood. Existing models for erythropoiesis do not include a central role for the ubiquitous iron storage protein ferritin; one model proposes that incoming endosomal Fe bound to transferrin enters the cytoplasm through an ion transporter after reduction to Fe and is taken up into mitochondria through mitoferrin-1 transporter. Here, we apply a dual three-dimensional imaging and spectroscopic technique, based on scanned electron probes, to measure Fe in human hematopoietic stem cells. After seven days in culture, we observe cells displaying a highly specialized architecture with anchored clustering of mitochondria and massive accumulation of nanoparticles containing high iron concentrations localized to lysosomal storage depots, identified as ferritin. We hypothesize that lysosomal ferritin iron depots enable continued heme production after expulsion of most of the cellular machinery.
在哺乳动物红细胞生成这一精细调控的过程中，不稳定铁池进入线粒体以生成血红素的途径尚不清楚。现有的红细胞生成模型并未赋予普遍存在的铁储存蛋白铁蛋白核心作用；一种模型提出，与转铁蛋白结合的内吞铁在还原为亚铁后通过离子转运体进入细胞质，并通过线粒体铁转运蛋白-1转运体被摄取到线粒体中。在此，我们应用基于扫描电子探针的三维成像和光谱联用技术，来测量人类造血干细胞中的铁。培养七天后，我们观察到细胞呈现出高度特化的结构，线粒体呈锚定聚集状态，且含有高铁浓度的纳米颗粒大量积累，这些纳米颗粒定位于溶酶体储存库，经鉴定为铁蛋白。我们推测，溶酶体铁蛋白铁库能够在大多数细胞机制排出后继续生成血红素。
