收稿日期: 2022-07-12
录用日期: 2022-12-16
网络出版日期: 2023-03-28
基金资助
国家自然科学基金(92059205)
Research progress in ferroptosis regulation in the treatment of liver diseases
Received date: 2022-07-12
Accepted date: 2022-12-16
Online published: 2023-03-28
Supported by
National Natural Science Foundation of China(92059205)
铁死亡是由于脂质活性氧自由基累积造成的细胞死亡，以铁依赖的脂质双分子层氧化性损伤为特征。铁积累和脂质过氧化是铁死亡过程中的关键标志。铁稳态、氧化还原稳态、脂质合成等过程失调可影响铁死亡。目前已报道铁死亡的主要调控轴包括胱氨酸/谷氨酸转运体（System Xc-）-谷胱甘肽（glutathione，GSH）-谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）轴、辅酶Q10（coenzyme Q10，CoQ10）-铁死亡抑制蛋白（ferroptosis suppressor protein 1，FSP1）-泛醇轴、GTP环化水解酶1（GTP cyclohydrolase 1，GCH1）-四氢生物蝶呤（tetrahydrobiopterin，BH4）-二氢叶酸还原酶（dihydrofolate reductase，DHFR）-磷脂轴、二氢乳清酸脱氢酶（dehydrogenase，DHODH）-泛醇轴等。铁死亡被视为重要的细胞死亡形式，在肝细胞癌、肝缺血再灌注损伤、脂肪性肝炎、肝纤维化、肝硬化和肝脏代谢病等多种疾病中发挥重要的作用，清晰阐释铁死亡的分子机制可为上述肝脏疾病的治疗提供潜在靶点。因此，该综述主要概括和探讨铁死亡的分子特征、相关生物学过程、调控途径，以及调控铁死亡在肝脏疾病治疗中的研究现状。
陈晨 , 程卓安 , 王存 , 夏强 . 铁死亡调控在肝脏疾病治疗中的研究进展[J]. 上海交通大学学报（医学版）, 2023 , 43(3) : 365 -373 . DOI: 10.3969/j.issn.1674-8115.2023.03.013
Ferroptosis is a form of cell death that results from accumulation of lipid reactive oxygen species, marked by iron-dependent oxidative damage of phospholipids. Accumulation of iron and lipid hydroperoxides are hallmarks of ferroptosis. Diverse biological contexts, including iron handling, redox homeostasis, imbalance of lipid synthesis, participate in ferroptosis. Mechanistically, pathways of ferroptosis regulation involving System Xc--glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis, coenzyme Q10 (CoQ10)-ferroptosis suppressor protein 1 (FSP1)-ubiquinol axis, GTP cyclohydrolase 1 (GCH1)-tetrahydrobiopterin (BH4)-dihydrofolate reductase (DHFR) axis, dehydrogenase (DHODH)-ubiquinol axis have been discovered. Ferroptosis has been implicated in multiple liver diseases, such as hepatocellular carcinoma, liver ischemia-reperfusion injury, steatohepatitis, liver fibrosis, cirrhosis and liver metabolic diseases. Elucidating its mechanism offers various tractable nodes for therapeutic intervention. Here, we summarize insights into the molecular characteristics, biological processes, regulatory pathways of ferroptosis and its recent advances in the treatment of liver diseases.
Key words： ferroptosis; liver disease; lipid peroxidation
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