Sun Li-Li, He Hai-Yan, Li Wei, Jin Wei-Lin, Wei Yi-Ju
School of Life Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
Biomark Res. 2024 Sep 2;12(1):94. doi: 10.1186/s40364-024-00645-2.
Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due to the accumulation of lipid peroxides in response to various stimuli, such as high levels of iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial in regulating ferroptosis. The solute carrier transporters (SLCs) family, known as the "metabolic gating" of cells, is responsible for transporting intracellular nutrients and metabolites. Recent studies have highlighted the significant role of SLCs family members in ferroptosis by controlling the transport of various nutrients. Here, we summarized the function and mechanism of SLCs in ferroptosis regulated by ion, metabolic control of nutrients, and multiple signaling pathways, with a focus on SLC-related transporters that primarily transport five significant components: glucose, amino acid, lipid, trace metal ion, and other ion. Furthermore, the potential clinical applications of targeting SLCs with ferroptosis inducers for various diseases, including tumors, are discussed. Overall, this paper delves into the novel roles of the SLCs family in ferroptosis, aiming to enhance our understanding of the regulatory mechanisms of ferroptosis and identify new therapeutic targets for clinical applications.
铁死亡是一种新型的程序性细胞死亡形式，由各种刺激（如高铁水平、氧化应激、代谢紊乱等）导致脂质过氧化物积累，进而损伤脂质膜所引起。糖、脂质、氨基酸和铁代谢在调节铁死亡过程中至关重要。溶质载体转运蛋白（SLCs）家族，被誉为细胞的“代谢闸门”，负责转运细胞内的营养物质和代谢产物。最近的研究强调了SLCs家族成员通过控制各种营养物质的转运在铁死亡中的重要作用。在此，我们总结了SLCs在铁死亡中的功能和机制，包括离子调节、营养物质的代谢控制以及多种信号通路，重点关注主要转运五种重要成分（葡萄糖、氨基酸、脂质、微量金属离子和其他离子）的SLC相关转运蛋白。此外，还讨论了使用铁死亡诱导剂靶向SLCs治疗包括肿瘤在内的各种疾病的潜在临床应用。总体而言，本文深入探讨了SLCs家族在铁死亡中的新作用，旨在加深我们对铁死亡调节机制的理解，并确定新的临床应用治疗靶点。
