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The Role of NCOA4-Mediated Ferritinophagy in Health and Disease

Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Institute of Medicine, Room 221, 4 Blackfan Circle, Boston, MA 02215, USA
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Pharmaceuticals 2018, 11(4), 114; https://doi.org/10.3390/ph11040114
Received: 8 September 2018 / Revised: 17 October 2018 / Accepted: 19 October 2018 / Published: 23 October 2018
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
Nuclear receptor coactivator 4 (NCOA4) is a selective cargo receptor that mediates the autophagic degradation of ferritin (“ferritinophagy”), the cytosolic iron storage complex. NCOA4-mediated ferritinophagy maintains intracellular iron homeostasis by facilitating ferritin iron storage or release according to demand. Ferritinophagy is involved in iron-dependent physiological processes such as erythropoiesis, where NCOA4 mediates ferritin iron release for mitochondrial heme synthesis. Recently, ferritinophagy has been shown to regulate ferroptosis, a newly described form of iron-dependent cell death mediated by excess lipid peroxidation. Dysregulation of iron metabolism and ferroptosis have been described in neurodegeneration, cancer, and infection, but little is known about the role of ferritinophagy in the pathogenesis of these diseases. Here, we will review the biochemical regulation of NCOA4, its contribution to physiological processes and its role in disease. Finally, we will discuss the potential of activating or inhibiting ferritinophagy and ferroptosis for therapeutic purposes. View Full-Text
Keywords: NCOA4; ferritinophagy; iron homeostasis; erythropoiesis; ferroptosis; cancer NCOA4; ferritinophagy; iron homeostasis; erythropoiesis; ferroptosis; cancer
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Santana-Codina, N.; Mancias, J.D. The Role of NCOA4-Mediated Ferritinophagy in Health and Disease. Pharmaceuticals 2018, 11, 114.

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