Ge Ting, Wang Yang, Han Yiwen, Bao Xiaofeng, Lu Chunfeng
School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Cell Biochem Biophys. 2025 Jun;83(2):1445-1464. doi: 10.1007/s12013-024-01611-3. Epub 2024 Nov 14.
Ferroptosis, a newly discovered mode of cell death, is a type of iron-dependent regulated cell death characterized by intracellular excessive lipid peroxidation and imbalanced redox. As the liver is susceptible to oxidative damage and the abnormal iron accumulation is a major feature of most liver diseases, studies on ferroptosis in the field of liver diseases are of great interest. Studies show that targeting the key regulators of ferroptosis can effectively alleviate or even reverse the deterioration process of liver diseases. System Xc and glutathione peroxidase 4 are the main defense regulators of ferroptosis, while acyl-CoA synthetase long chain family member 4 is a key enzyme causing peroxidation in ferroptosis. Generally speaking, ferroptosis should be suppressed in alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver injury, while it should be induced in liver fibrosis and hepatocellular carcinoma. In this review, we summarize the main regulators involved in ferroptosis and then the mechanisms of ferroptosis in different liver diseases. Treatment options of drugs targeting ferroptosis are further concluded. Determining different triggers of ferroptosis can clarify the mechanism of ferroptosis occurs at both physiological and pathological levels.
铁死亡是一种新发现的细胞死亡方式，是一种铁依赖性的调节性细胞死亡，其特征在于细胞内过度的脂质过氧化和氧化还原失衡。由于肝脏易受氧化损伤，且铁异常蓄积是大多数肝脏疾病的主要特征，因此肝脏疾病领域中铁死亡的研究备受关注。研究表明，靶向铁死亡的关键调节因子可有效缓解甚至逆转肝脏疾病的恶化进程。系统Xc⁻和谷胱甘肽过氧化物酶4是铁死亡的主要防御调节因子，而酰基辅酶A合成酶长链家族成员4是铁死亡中引起过氧化的关键酶。一般来说，在酒精性肝病、非酒精性脂肪性肝病和药物性肝损伤中应抑制铁死亡，而在肝纤维化和肝细胞癌中应诱导铁死亡。在这篇综述中，我们总结了参与铁死亡的主要调节因子，然后阐述了不同肝脏疾病中铁死亡的机制。进一步总结了靶向铁死亡的药物治疗选择。确定铁死亡的不同触发因素可以阐明铁死亡在生理和病理水平上发生的机制。
