Guo Nan, Chen Yan, Zhang Yuhong, Deng Yonghao, Zeng Fancai, Li Xiang
Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Southwest Medical University, Luzhou, China.
Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Front Oncol. 2022 Mar 3;12:798304. doi: 10.3389/fonc.2022.798304. eCollection 2022.
Ferroptosis is a recently discovered category of programmed cell death. It is much different from other types of cell death such as apoptosis, necrosis and autophagy. The main pathological feature of ferroptosis is the accumulation of iron-dependent lipid peroxidation. The typical changes in the morphological features of ferroptosis include cell volume shrinkage and increased mitochondrial membrane area. The mechanisms of ferroptosis may be mainly related to lipid peroxidation accumulation, imbalance in amino acid antioxidant system, and disturbance of iron metabolism. Besides, hypoxia-inducible factor (HIF), nuclear factor-E2-related factor 2 (Nrf2), and p53 pathway have been demonstrated to be involved in ferroptosis. At present, the molecular mechanisms of ferroptosis pathway are still unmapped. In this review, an outlook has been put forward about the crucial role of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) in the regulation of ferroptosis. APEX1 plays an important role in the regulation of intracellular redox balance and can be used as a potential inhibitor of ferroptotic cell death. Bioinformatics analysis indicated that the mRNA level of APEX1 is decreased in cases of ferroptosis triggered by erastin. Besides, it was found that there was a significant correlation between and genes in the ferroptosis pathway. We have discussed the possibility to employ APEX1 inducers or inhibitors in the regulation of ferroptosis as a new strategy for the treatment of various human diseases.
铁死亡是最近发现的一种程序性细胞死亡类型。它与其他类型的细胞死亡如凋亡、坏死和自噬有很大不同。铁死亡的主要病理特征是铁依赖性脂质过氧化的积累。铁死亡形态学特征的典型变化包括细胞体积缩小和线粒体膜面积增加。铁死亡的机制可能主要与脂质过氧化积累、氨基酸抗氧化系统失衡以及铁代谢紊乱有关。此外，缺氧诱导因子（HIF）、核因子E2相关因子2（Nrf2）和p53途径已被证明参与铁死亡。目前，铁死亡途径的分子机制仍未明确。在这篇综述中，对脱嘌呤/脱嘧啶内切脱氧核糖核酸酶1（APEX1）在铁死亡调节中的关键作用提出了展望。APEX1在调节细胞内氧化还原平衡中起重要作用，可作为铁死亡细胞死亡的潜在抑制剂。生物信息学分析表明，在由erastin引发的铁死亡病例中，APEX1的mRNA水平降低。此外，还发现与铁死亡途径中的基因之间存在显著相关性。我们讨论了使用APEX1诱导剂或抑制剂来调节铁死亡作为治疗各种人类疾病的新策略的可能性。
