《生命科学》 2024, 36(8): 1030-1039

CNC-bZIP转录因子家族成员调节细胞铁死亡的研究进展

丁之冉¹ , 郑孟华¹ , 杨雪松² , 邱　露³ , 任勇刚^1,2,*

¹川北医学院基础医学与法医学院，南充 637100 ²川北医学院附属医院， 南充 637100 ³郑州大学第一附属医院病理科，郑州 450052

摘　要：

铁死亡是铁依赖的膜脂质过氧化程序性细胞死亡，靶向铁死亡已成为癌症、神经退行性病变等多种疾病的潜在治疗方法。铁死亡主要受胱氨酸/ 谷氨酸反向转运蛋白、谷胱甘肽过氧化物酶、铁转运蛋白等抗氧化和铁转运体系调控，其中抗氧化系统的失调或失能被认为是诱发铁死亡的重要因素。CNC-bZIP转录因子家族成员在机体氧化还原稳态、蛋白质稳态、糖脂代谢稳态中发挥重要感知和调控作用，通过调节氧化还原平衡和铁代谢稳态参与细胞铁死亡进程。该文详细阐述了NFE2L1、NFE2L2、NFE2L3 等CNCbZIP转录因子家族成员在调控细胞铁死亡进程中的具体作用，系统性地梳理了这些转录因子调节细胞铁死亡分子机制的共性与差异，为靶向氧化还原稳态防治细胞铁死亡相关疾病提供分子靶标和理论参考。

通讯作者：任勇刚 , Email:rygqfyy@nsmc.edu.cn

Progress in the regulation of cell ferroptosis through members of the CNC-bZIP transcription factor family

DING Zhi-Ran¹ , ZHENG Meng-Hua¹ , YANG Xue-Song² , QIU Lu³ , REN Yong-Gang^1,2,*

¹School of Basic Medical Sciences and Forensic Medicine, North Sichuan Medical College, Nanchong 637100, China ²Affiliated Hospital of North Sichuan Medical College, Nanchong 637100, China ³Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

Abstract:

Ferroptosis is iron-dependent programmed cell death by membrane lipid peroxidation, and targeting ferroptosis has emerged as a potential therapeutic approach for a variety of diseases, including cancer and neurodegenerative pathologies. Ferroptosis is mainly regulated by antioxidant and iron transport systems, such as cystine/glutamate reverse transporter proteins, glutathione peroxidase and iron transporter proteins, with dysregulation or dysfunction of antioxidant systems thought to be an important factor in the induction of ferroptosis. Members of the CNC-bZIP transcription factor family play important sensing and regulatory roles in organismal redox homeostasis, protein homeostasis and glycolipid metabolism homeostasis, and are involved in the process of cellular ferroptosis by regulating redox homeostasis and iron metabolism homeostasis. In this paper, the specific roles of CNC-bZIP transcription factors, such as NFE2L1, NFE2L2 and NFE2L3, in regulating the process of cellular ferroptosis are elaborated in detail, and the similarities and differences in the molecular mechanisms of cellular ferroptosis regulated by CNC-bZIP transcription factors are systematically sorted out to provide molecular targets and theoretical references for targeting redox homeostasis to prevent and control cellular ferroptosis-related diseases.

Communication Author：REN Yong-Gang , Email:rygqfyy@nsmc.edu.cn