Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Korea.
Department of Functional Genomics, University of Science and Technology (UST), Daejeon, 34141, Korea.
Exp Mol Med. 2023 Aug;55(8):1620-1631. doi: 10.1038/s12276-023-01077-y. Epub 2023 Aug 23.
Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular diseases, neurodegeneration, liver disease, and cancer. Although polyunsaturated fatty acids (PUFAs) in membrane phospholipids are preferentially oxidized, saturated/monounsaturated fatty acids (SFAs/MUFAs) also influence lipid peroxidation and ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs and PUFAs and how they control fatty acid pools via fatty acid uptake and β-oxidation, impacting ferroptosis. Furthermore, we discuss how fatty acids are stored in different lipids, such as diacyl or ether phospholipids with different head groups; triglycerides; and cholesterols. Moreover, we explain how these fatty acids are released from these molecules. In summary, we provide an integrated view of the diverse and dynamic metabolic processes in the context of ferroptosis by revisiting lipidomic studies. Thus, this review contributes to the development of therapeutic strategies for ferroptosis-related diseases.
铁死亡是一种受调控的细胞死亡形式，其特征是铁依赖性脂质过氧化。这个过程导致了多种人类疾病中的细胞和组织损伤，如心血管疾病、神经退行性疾病、肝脏疾病和癌症。尽管膜磷脂中的多不饱和脂肪酸（PUFAs）优先被氧化，但饱和/单不饱和脂肪酸（SFAs/MUFAs）也会影响脂质过氧化和铁死亡。在这篇综述中，我们首先解释了细胞如何差异合成 SFA/MUFAs 和 PUFAs，以及它们如何通过脂肪酸摄取和β-氧化来控制脂肪酸池，从而影响铁死亡。此外，我们讨论了脂肪酸如何以不同的头基储存在不同的脂质中，如二酰基或醚磷脂；甘油三酯；和胆固醇。此外，我们解释了这些脂肪酸是如何从这些分子中释放出来的。总之，我们通过重新审视脂质组学研究，提供了一个关于铁死亡背景下多样化和动态代谢过程的综合观点。因此，这篇综述为铁死亡相关疾病的治疗策略的发展做出了贡献。
