Use of dual-electron probes reveals the role of ferritin as an iron depot in ex vivo erythropoiesis.
| Autor: | Aronova MA; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, USA., Noh SJ; Penta Medix Co., Ltd., Seongnam, Gyeonggi-do, Republic of Korea., Zhang G; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, USA., Byrnes C; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA., Meier ER; Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA., Kim YC; Computational Biophysics, Center for Materials Physics and Technology, US Naval Research Laboratory, Washington, DC, USA., Leapman RD; Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, USA. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2021 Jul 24; Vol. 24 (8), pp. 102901. Date of Electronic Publication: 2021 Jul 24 (Print Publication: 2021). |
| DOI: | 10.1016/j.isci.2021.102901 |
| Abstrakt: | 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 3+ bound to transferrin enters the cytoplasm through an ion transporter after reduction to Fe 2+ 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 3+ in ex vivo 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. Competing Interests: The authors declare no competing financial interests. |
| Databáze: | MEDLINE |
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