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长链酯酰辅酶A合成酶4介导铁死亡的发生机制

The Mechanism of Long-Chain acyl-CoA Synthetase 4-mediated Ferroptosis
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摘要 铁死亡(ferroptosis)是一种铁和脂质过氧化依赖性的程序性死亡方式,触发铁死亡的必要条件是细胞内活性氧物质堆积到致死量。由脂质过氧化反应产生的脂质活性氧会作用于细胞膜上的脂质分子,导致脂质过氧化和膜损伤,因此脂质过氧化是铁死亡的显著特征。长链酯酰辅酶A合成酶4(long-chain acyl-CoA synthetase 4,ACSL4)在调节脂质代谢方面具有关键作用,其主要功能是将多不饱和脂肪酸酯化并插入膜磷脂中,从而加速脂质过氧化的发生并推动铁死亡。ACSL4介导的铁死亡主要受到转录、转录后和翻译后水平上的调控影响,在脂质过氧化依赖性的疾病中发挥着重要作用。本文旨在介绍铁死亡的发生机制,重点阐述了ACSL4受到的上游调控从而介导铁死亡的机制,为研究ACSL4介导铁死亡机制提供理论依据。 Ferroptosis is an iron and lipid peroxidation-dependent mode of programmed death,and it is triggered when the accumulation of reactive oxygen species reaches a lethal level within the cell.Lipid reactive oxygen species produced by lipid peroxidation act on lipid molecules on cell membranes,resulting in lipid peroxidation and membrane damage,so lipid peroxidation is a prominent feature of ferroptosis.Long-chain acyl-CoA synthetase 4(ACSL4)plays a crucial role in regulating lipid metabolism,primarily by esterifying polyunsaturated fatty acids and incorporating them into membrane phospholipids,thereby accelerating lipid peroxidation and driving ferroptosis.ACSL4-mediated ferroptosis is mainly regulated at transcriptional,post-transcriptional,and post-translational levels and plays an important role in lipid peroxidation-dependent diseases.The purpose of this study is to elucidate the mechanisms underlying ferroptosis,focusing on the upstream regulation of ACSL4 and consequently mechanism of ferroptosis,providing a theoretical basis for investigation into the mechanisms of ACSL4-mediated ferroptosis.
作者 付红玉 李玥 崔晗 李玖芝 许琬雪 王曦 樊瑞锋 FU Hongyu;LI Yue;CUI Han;LI Jiuzhi;XU Wanxue;WANG Xi;FAN Ruifeng(College of Veterinary Medicine,Shandong Agricultural University,Tai’an 271017,China)
出处 《畜牧兽医学报》 CAS CSCD 北大核心 2024年第9期3792-3801,共10页 ACTA VETERINARIA ET ZOOTECHNICA SINICA
基金 国家自然科学基金资助项目(32273088,31902330)。
关键词 ACSL4 铁死亡 脂质过氧化 上游调控机制 long-chain acyl-CoA synthetase 4 ferroptosis lipid peroxidation upstream regulation mechanism
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