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. 2023 Dec 28;12:e83103. doi: 10.7554/eLife.83103

Figure 10. Putative function of erythroblast iron trafficking in health and in MDS before and after DFP treatment.

Figure 10.

Erythroblast iron uptake is mediated by TFR1 via endocytosis of clathrin-coated pits. In addition, erythroblast ferritin iron delivery is an obligatory step in erythropoiesis, and chaperones, i.e., PCBP1 and PCBP2, deliver iron to ferritin while NCOA4 enable iron extraction from ferritin, leading to iron utilization for hemoglobin synthesis in the mitochondria (A). In conditions of expanded erythropoiesis, such as MDS (B), more TFR1 results in increased iron uptake, resulting in decreased PCBP1 and NCOA4; yet no change in ferritin storage. Treatment with DFP restores erythroblast iron trafficking with decreased TFR1, increased PCBP1 and NCOA4, and increased ferritin concentration (C). We propose a model in which altered iron delivery to the mitochondria correlates with increased erythroblast survival and proliferation and decreased erythroid differentiation, causing ineffective erythropoiesis in MDS, ameliorated in response to DFP. Abbreviations: WT = wild type; MDS = myelodysplastic syndrome; DFP = deferiprone; TF = transferrin; TFR1 = transferrin receptor 1; PCBP1/2=Poly(rC)-binding protein 1 and 2; NCOA4=nuclear receptor coactivator 4; Hb = hemoglobin.