精胺是一种抑制铁死亡的内源性铁螯合剂
精胺是一种抑制铁死亡的内源性铁螯合剂，这一成果由中山大学中山医学院李隽小组经过不懈努力而取得。这一研究成果发表在2026年6月3日出版的国际学术期刊《自然》上。
在这里，该团队确定精胺-一种衍生自精胺的多胺-作为内源性铁螯合剂，直接抑制铁死亡。结合代谢组学、稳定同位素示踪和精胺与Fe2+离子相互作用的生物物理研究，该研究组证明醛脱氢酶18家族成员A1 （ALDH18A1）促进了另一种谷氨酰胺依赖的精胺合成途径。这一过程限制了肝细胞癌中铁的可用性和脂质过氧化。基因或药理学抑制ALDH18A1（通过敲除、短发卡RNA递送主题腺相关病毒（AAV）或小分子抑制剂YG1702）可触发铁凋亡，并损害自发和化学诱导的肝癌发生。相反，补充精胺可以防止死铁相关的缺血再灌注损伤，包括肝、肠和肾等多个组织。这些发现揭示了精胺介导的铁螯合抑制铁死亡的病理生理相关代谢回路。
研究人员表示，铁死亡是一种由脂质过氧化引起的铁依赖性细胞死亡。
附：英文原文
Title: Spermine is an endogenous iron chelator that inhibits ferroptosis
Author: Li, Man, Yu, Xuexin, Ouyang, Shuqin, Chen, Xiaohong, Yu, Huiqi, Liu, Yuanji, Li, Ziwen, Yu, Chunhua, Kang, Rui, Gaillet, Christine, Colombeau, Ludovic, Rodriguez, Raphal, Song, Libing, Kroemer, Guido, Tang, Daolin, Li, Jun
Issue&Volume: 2026-06-03
Abstract: Ferroptosis is an iron-dependent form of cell death driven by lipid peroxidation1. Here we identify spermine—a polyamine derived from spermidine2—as an endogenous iron chelator that directly suppresses ferroptosis. Integrating metabolomics, stable isotope tracing and biophysical studies of the interaction between spermine and Fe2+ ions, we demonstrate that aldehyde dehydrogenase 18 family member A1 (ALDH18A1) promotes an alternative glutamine-dependent pathway for de novo spermine synthesis. This process limits iron availability and lipid peroxidation in hepatocellular carcinoma. Genetic or pharmacological inhibition of ALDH18A1—through knockout, short hairpin RNA delivered using adeno-associated virus (AAV), or the small molecule inhibitor YG1702—triggers ferroptosis and impairs both spontaneous and chemically induced hepatocarcinogenesis. Conversely, supplementation of spermine protects against ferroptosis-associated ischaemia–reperfusion injury across multiple tissues, including the liver, intestine and kidneys. These findings uncover a pathophysiologically relevant metabolic circuit in which spermine-mediated iron chelation suppresses ferroptosis.
DOI: 10.1038/s41586-026-10597-2
Source: https://www.nature.com/articles/s41586-026-10597-2
期刊信息
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
投稿链接：http://www.nature.com/authors/submit_manuscript.html
