双硫死亡：硫代谢异常驱动的新型细胞死亡机制
熊逍鹤 季平^*

重庆医科大学，重庆，400016；

摘要：细胞死亡作为维持机体稳态的核心机制，其形式与调控网络持续拓展。近年来，基于代谢组学与细胞生物学交叉研究，双硫死亡（Disulfidptosis）作为一种新型程序性细胞死亡方式被揭示，其发生机制与硫代谢异常密切相关。该过程由SLC7A11高表达或葡萄糖缺乏引发的胱氨酸异常积累驱动，导致细胞内二硫键应激，促使F-肌动蛋白丝间形成异常交联，最终引发细胞骨架瓦解与膜结构崩解。研究表明，双硫死亡在肿瘤细胞中呈现显著的代谢依赖性，尤其与硫代谢失衡及氧化还原稳态紊乱存在深层关联。靶向SLC7A11与葡萄糖代谢的联合干预策略（如GLUT1抑制剂BAY-876）在肾癌、乳腺癌等模型中展现出选择性杀伤效应，但其临床应用仍受限于肿瘤异质性、代谢可塑性及正常组织毒性。进一步研究发现，氧化还原通路与细胞骨架动力学调控网络通过正反馈机制影响双硫死亡进程，提示多通路协同靶向的重要性。未来研究需整合多组学技术解析双硫死亡与其他死亡模式的交互作用，并开发基于肿瘤微环境代谢特征的精准干预策略。双硫死亡的发现不仅丰富了细胞死亡理论体系，也为肿瘤代谢治疗提供了全新的分子靶点与转化方向。

关键词：双硫死亡；硫代谢；半胱氨酸；SLC7A11；肿瘤治疗

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