铁蛋白
脂质过氧化
程序性细胞死亡
GPX4
化学
细胞生物学
细胞保护
活性氧
小分子
抗氧化剂
氧化应激
生物化学
生物
细胞凋亡
超氧化物歧化酶
谷胱甘肽过氧化物酶
作者
Wei Yang,Bo Mu,Jianxin You,Chuanshan Tian,Huachao Bin,Zhiqiang Xu,Liting Zhang,Ronggang Ma,Ming Wu,Guo Zhang,Chong Huang,Linli Li,Zhenhua Shao,Lunzhi Dai,Laurent Désaubry,Shengyong Yang
标识
DOI:10.1038/s41467-022-35294-2
摘要
Ferroptosis is a new type of programmed cell death characterized by iron-dependent lipid peroxidation. Ferroptosis inhibition is thought as a promising therapeutic strategy for a variety of diseases. Currently, a majority of known ferroptosis inhibitors belong to either antioxidants or iron-chelators. Here we report a new ferroptosis inhibitor, termed YL-939, which is neither an antioxidant nor an iron-chelator. Chemical proteomics revealed the biological target of YL-939 to be prohibitin 2 (PHB2). Mechanistically, YL-939 binding to PHB2 promotes the expression of the iron storage protein ferritin, hence reduces the iron content, thereby decreasing the susceptibility to ferroptosis. We further showed that YL-939 could substantially ameliorate liver damage in a ferroptosis-related acute liver injury model by targeting the PHB2/ferritin/iron axis. Overall, we identified a non-classical ferroptosis inhibitor and revealed a new regulation mechanism of ferroptosis. These findings may present an attractive intervention strategy for ferroptosis-related diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI