长链酰基辅酶A合成酶4的生物学及病理学功能研究进展

Advances in biological and pathological functions of long-chain acyl-CoA synthetase 4

长链酰基辅酶A合成酶4 (long-chain acyl-CoA synthetase 4, ACSL4)是多不饱和脂肪酸(polyunsaturated fatty acid, PUFA)代谢的重要催化酶,广泛存在于合成类固醇的组织中。以往研究报道ACSL4功能多聚焦于调节脂代谢。近期研究表明ACSL4与机体胰岛素分泌、骨骼肌蛋白质代谢及机体炎症反应等多种生物学过程密切相关,且ACSL4可能通过介导铁死亡调控癌症和缺血性脑卒中及急性肾损伤的发生发展。此外,ACSL4在非酒精性脂肪肝病及肝癌中表达失调,并通过上调mTOR磷酸化或c-Myc进而促进肝细胞增殖,提示ACSL4可能是多种疾病的治疗靶点。本文主要对ACSL4的生理及病理作用进行综述,以期为相关研究和治疗提供理论依据。

ACSL4(long-chain acyl-CoA synthetase 4)is an important catalase for polyunsaturated fatty acid(PUFA)metabolism and is widely found in tissues where steroids are synthesized.Previous studies on ACSL4 mostly focused on its roles in regulating lipid metabolism.However,it has shown recently that ACSL4 is closely related to various biological processes,such as insulin secretion,skeletal muscle protein metabolism and inflammatory response of the body,and ACSL4 may regulate the development of cancer,ischemic stroke and acute kidney injury by mediating ferroptosis.In addition,ACSL4 is dysregulated in nonalcoholic fatty liver disease and hepatocellular carcinoma,and promotes hepatocyte proliferation by upregulating mTOR phosphorylation or c-Myc,suggesting that ACSL4 may be a therapeutic target for a variety of diseases.In this paper,we mainly review the newly reported physiological and pathological roles of ACSL4,aiming to provide theoretical basis for related research and treatment of diseases.