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The flux of iron through ferritin in erythrocyte development

Philpott, Caroline, C.

Current Opinion in Hematology: May 2018 - Volume 25 - Issue 3 - p 183–188
doi: 10.1097/MOH.0000000000000417
ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas

Purpose of review Terminal differentiation of erythropoietic progenitors requires the rapid accumulation of large amounts of iron, which is transported to the mitochondria, where it is incorporated into heme. Ferritin is the sole site of iron storage present in the cytosol. Yet the role of iron accumulation into ferritin in the context of red cell development had not been clearly defined. Early studies indicated that at the onset of terminal differentiation, iron initially accumulates in ferritin and precedes heme synthesis. Whether this accumulation is physiologically important for red cell development was unclear until recent studies defined an obligatory pathway of iron flux through ferritin.

Recent findings The iron chaperone functions of poly rC-binding protein 1 (PCBP1) and the autophagic cargo receptor for ferritin, nuclear co-activator 4 (NCOA4) are required for the flux of iron through ferritin in developing red cells. In the absence of these functions, iron delivery to mitochondria for heme synthesis is impaired.

Summary The regulated trafficking of iron through ferritin is important for maintaining a consistent flow of iron to mitochondria without releasing potentially damaging redox-active species in the cell. Other components of the iron trafficking machinery are likely to be important in red cell development.

Genetics and Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to Caroline C. Philpott, Genetics and Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg 10, Room 9B-16, 10 Center Drive MSC 1800, Bethesda, MD 20892, USA. Tel: +1 301 435 4018; e-mail: carolinep@mail.nih.gov

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