The Role of NCOA4-Mediated Ferritinophagy in Health and Disease

Pharmaceuticals

Naiara Santana-Codina¹  Joseph D. Mancias¹ 

[1] 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;

关键词: NCOA4;    ferritinophagy;    iron homeostasis;    erythropoiesis;    ferroptosis;    cancer;   

DOI  :  10.3390/ph11040114

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown