Acyl-CoA synthase ACSL4:an essential target in ferroptosis and fatty acid metabolism  

作　　者：Kaiyue Ding Chongbin Liu Li Li Ming Yang Na Jiang Shilu Luo Lin Sun 

机构地区：[1]Department of Nephrology,The Second Xiangya Hospital,Central South University,Changsha,Hunan 410000,China [2]Hunan Key Laboratory of Kidney Disease and Blood Purification,Changsha,Hunan 410000,China

出　　处：《Chinese Medical Journal》2023年第21期2521-2537,共17页中华医学杂志（英文版）

基　　金：supported by the Key Program of General Program of the National Natural Science Foundation of China(NSFC)(No.81730018);Natural Science Foundation of Hunan Province(No.2021JC0003)

摘　　要：Long-chain acyl-coenzyme A(CoA)synthase 4(ACSL4)is an enzyme that esterifies CoA into specific polyunsaturated fatty acids,such as arachidonic acid and adrenic acid.Based on accumulated evidence,the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation.Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids;ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis,respectively.In addition,ACSL4 is an essential regulator of fatty acid(FA)metabolism.ACSL4 remodels the phospholipid composition of cell membranes,regulates steroidogenesis,and balances eicosanoid biosynthesis.In addition,ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology.Because it facilitates the cross-talk between ferroptosis and FA metabolism,ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries.In this review,we focus on the structure,biological function,and unique role of ASCL4 in various human diseases.Finally,we propose that ACSL4 might be a potential therapeutic target.

关 键 词：Long-chain acyl-coenzyme A(CoA)synthase 4(ACSL4) Ferroptosis Fatty acid metabolism Cancer ISCHEMIA/REPERFUSION Metabolic diseases 

分 类 号：R730[医药卫生—肿瘤]