Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China.
Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China.
Cell Death Dis. 2020 Jul 9;11(7):518. doi: 10.1038/s41419-020-2732-5.
Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system x have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.
铁死亡是一种铁依赖性和脂质毒性依赖性的细胞死亡形式（RCD）。它在形态和生化上与其他细胞死亡的特征不同。近年来，由于铁死亡在多种病理学中的作用，包括癌症、神经退行性疾病和急性肾损伤，这种模式受到了广泛的研究。铁死亡的失调也与各种肝脏疾病有关，其修饰可能提供一个有希望和有吸引力的治疗概念。事实上，靶向铁死亡可能会阻止几种肝脏疾病的病理生理进展，如血色病、非酒精性脂肪性肝炎和乙醇诱导的肝损伤。相反，增强铁死亡可能会促进索拉非尼诱导的铁死亡，并为肝癌的联合治疗铺平道路。谷胱甘肽过氧化物酶 4（GPx4）和系统 x 已被确定为介导铁死亡途径的关键因素。最近还观察到了多种信号通路。铁死亡与其他形式的 RCD 之间的联系是复杂而引人注目的，这一领域的发现增进了我们对细胞存活和命运的理解。在这篇综述中，我们总结了铁死亡的核心分子机制，描述了铁死亡在非癌症肝脏疾病中的作用，并讨论了将铁死亡作为一种治疗策略的潜力。
