The Role of NCOA4-Mediated Ferritinophagy in Health and Disease.

The Role of NCOA4-Mediated Ferritinophagy in Health and Disease.
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DOI:
10.3390/ph11040114
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发表时间:
2018-10-23
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
Mancias JD
Mancias JD
中科院分区:
其他
文献类型:
--
作者:
Santana-Codina N;Mancias JD

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核受体共激活因子4 (NCOA4)是一种选择性货物受体,可介导铁蛋白的自噬降解(“铁蛋白自噬”),即胞质铁储存复合物。ncoa4介导的铁蛋白自噬通过促进铁蛋白铁根据需要储存或释放来维持细胞内铁稳态。铁蛋白自噬参与铁依赖的生理过程,如红细胞生成,其中NCOA4介导铁蛋白铁释放,用于线粒体血红素合成。最近,铁蛋白自噬已被证明可调节铁凋亡,铁凋亡是一种由过量脂质过氧化介导的铁依赖性细胞死亡的新形式。在神经退行性疾病、癌症和感染中已经发现了铁代谢失调和铁凋亡,但对铁蛋白吞噬在这些疾病的发病机制中的作用知之甚少。在此,我们将对NCOA4的生化调控、对生理过程的贡献及其在疾病中的作用进行综述。最后,我们将讨论激活或抑制铁蛋白吞噬和铁下垂的潜在治疗目的。
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.
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