铁自噬与铁死亡的关系及铁自噬相关疾病

Relationship between ferritinophagy and ferropotosis and ferritinophagy related diseases

铁自噬是一种选择性自噬,发挥维持细胞内铁稳态的重要作用。在铁自噬过程中,核受体辅激活因子4和铁蛋白构成复合物并于与自噬体融合,可靶向溶酶体降解铁蛋白而释放出游离铁供机体使用。铁自噬也是铁死亡的重要机制,当它过度激活时,可导致细胞内铁超载和致死性活性氧的堆积,造成大量细胞铁死亡。铁自噬通过调节细胞内铁稳态和致死性活性氧的生成,成为诱导铁死亡的上游机制,与脑缺血再灌注损伤、癌症、心血管系统等疾病的发生发展密切相关。因此,研究核受体辅激活因子4介导的铁自噬通路在铁死亡中的功能特征,了解铁自噬机制在不同疾病发展方向中的作用,可能为铁自噬相关疾病的治疗提供启示。本文将从铁自噬的机制及其调控因素、铁自噬与铁死亡的关系等方面论述铁自噬通路,着重探讨铁自噬在不同疾病发生发展中的作用,期望以铁自噬为切入点,为相关疾病的治疗提供新思路。

Ferritinophagy is a new type of autophagy,playing an important role in maintaining iron homeostasis in cells.In the process of ferritinophagy,a complex composed of nuclear receptor coactivator 4 and ferritin is fused with the autophagosome and targeted lysosomes to degrade ferritin to release free iron for body use.Ferritinophagy is also an important part of ferroptosis.When ferritinophagy is over activated,it can lead to intracellular iron overload and accumulation of lethal reactive oxygen species in cells,resulting in a large number of cell ferroptosis.Ferritinophagy has become a upstream mechanism inducing ferroptosis by regulating intracellular iron homeostasis and the generation of lethal reactive oxygen species,which is closely related to the occurrence and development of cerebral ischemia reperfusion injury,cancer,cardiovascular system and other diseases.Therefore,to study the functional characteristics of nuclear receptor coactivator 4 mediated ferritinophagy pathway in ferroptosis,and to understand the role of ferritinophagy mechanism in the development direction of different diseases,may provide implications for the treatment of ferritinophagy related diseases.This paper will discuss the pathway of ferritinophagy from the aspects of the mechanism and regulatory factors of ferritinophagy,the relationship between ferritinophagy and ferroptosis,and focus on the role of ferritinophagy in the occurrence and development of different diseases,hoping to provide new ideas for the treatment of related diseases by taking ferritinophagy as the starting point.