近日，山东大学基础医学院初波团队的最新研究提出了谷胱甘肽通过FSP1抑制铁下垂的非规范功能。相关论文于2026年10月6日发表于国际顶尖学术期刊《细胞》杂志上。

众所周知，谷胱甘肽（GSH）主要被谷胱甘肽过氧化物酶4（GPX4）利用，以减少过氧化的磷脂并防御铁死亡。然而，研究人员发现，GSH能强效保护多种GPX4敲除（KO）细胞免于铁死亡，从而表明存在一条GSH抑制铁死亡的替代途径。通过全基因组CRISPR-Cas9筛选，研究人员鉴定出铁死亡抑制蛋白1（FSP1）是介导GSH不依赖GPX4保护作用的关键因子。机制上，FSP1利用GSH生成还原型泛醌，后者清除氧化脂质并抑制铁死亡。抑制FSP1可在体外和体内消除这种GSH依赖性铁死亡保护。与NAD(P)H介导的泛醌还原不同，GSH通过FSP1刺激生成还原型泛醌不依赖于黄素腺嘌呤二核苷酸（FAD）。总之，该工作阐明了GSH介导铁死亡抑制的一种新机制，从而凸显了靶向GSH代谢可能有益于铁死亡相关疾病，无论其是否与GPX4相关。

附：英文原文

Title: A non-canonical function of glutathione to suppress ferroptosis via FSP1

Author: Jing Han, Yu-Dan Zhang, Shuo Liu, Li Yang, Shuang-Li Sun, Ben Zhang, Ao-Kun Liu, Ling-Fan Zhu, Rong Wang, Dan-Dan Song, Xiao Zhuang, Yi-Jia Gao, Jing-Xin Li, Wen-Fei Li, Rong-Rong He, Heng-Xing Zhou, Lu Yu, Shi-Qing Feng, Ren-Jie Chai, Bo Chu

Issue&Volume: 2026-10-06

Abstract: It is well established that glutathione (GSH) is mainly utilized by glutathione peroxidase 4 (GPX4) to diminish peroxidized phospholipids and defend against ferroptosis. However, we found that GSH robustly protects a variety of GPX4 knockout (KO) cells from ferroptosis, thus indicating that there is an alternative pathway for GSH to suppress ferroptosis. By carrying out genome-wide CRISPR-Cas9 screening, we identified that ferroptosis suppressor protein 1 (FSP1) is the key factor mediating the GPX4-independent protective effect of GSH. Mechanistically, FSP1 uses GSH to generate reduced ubiquinone, which scavenges oxidized lipids and suppresses ferroptosis. Inhibition of FSP1 abolishes this GSH-dependent ferroptosis protection both in vitro and in vivo. Distinct from NAD(P)H-mediated ubiquinone reduction, GSH-stimulated generation of reduced ubiquinone via FSP1 is independent of flavin adenine dinucleotide (FAD). Together, our work clarifies a new mechanism of GSH-mediated ferroptosis suppression, thus highlighting the potential that targeting GSH metabolism should be beneficial for ferroptosis-related diseases whether or not it is related to GPX4.

DOI: 10.1016/j.cell.2026.09.024

Source: https://www.cell.com/cell/abstract/S0092-8674(26)01126-8