脂酰辅酶A长链合成酶3及其相关疾病

脂滴(lipid droplets)是细胞内脂质贮存和调节细胞脂质稳态的重要细胞器,其表面具有多种脂滴相关蛋白质。长链酰基辅酶A合成酶家族的成员脂酰辅酶A长链合成酶3(acyl CoA long chain synthetase 3,ACSL3)即脂滴相关蛋白质的一种,也是生物合成过程中必需的酶之一。ACSL3广泛分布于大多数细胞中的脂滴表面,其在脂滴的合成、自噬的调节和细胞铁死亡等多种病理生理过程中发挥着不同的作用。此外,多项研究表明,ACSL3还广泛参与到多种疾病的发生发展,包括动脉粥样硬化、非酒精性脂肪肝病、糖尿病和肿瘤等。当前,国内对ACSL3的研究相对集中于ACSL3与动物育种和生长的关系,而对ACSL3在脂质代谢中的作用机制及其与疾病的关系鲜有报道。本文基于国内外对ACSL3的研究,对该基因的结构、在细胞脂代谢中的作用机制及其相关疾病进行归纳,进一步探究ACSL3在脂滴的合成、自噬、铁死亡过程中的作用,为防治动脉粥样硬化、非酒精性脂肪肝病、糖尿病(glucose)等多种ACSL3相关疾病提供新的理论依据。

Research Progress of ACSL3 and Related Diseases

Lipid droplets are important organelles that have the function of storing intracellular lipid and regulation of cell lipid homeostasis. A variety of lipid droplet-related proteins exists on the surface of lipid droplets. The acyl CoA long chain synthetase 3 (ACSL3) of the long chain acyl-CoA synthetase family is a kind of lipid droplet-related protein and an essential enzyme in the process of biosynthesis. ACSL3, which plays different roles in a variety of pathophysiological processes such as the synthesis of lipid droplets, the regulation of autophagy, and cell iron death, is widely distributed on the surface of lipid droplets in most cells. In addition, many studies have shown that ACSL3 is also widely involved in the occurrence and development of atherosclerosis, nonalcoholic fatty liver disease, diabetes, and tumors. At present, domestic research on ACSL3 is relatively focused on the relationship between ACSL3 and animal breeding and growth. However, the reports on the mechanism of ACSL3 in lipid metabolism and the relationship between ACSL3 and diseases are relatively rare. This article summarizes the structure of ACSL3 and its mechanism in cell lipid metabolism and related diseases, which may provide a new theoretical basis for the prevention and treatment of atherosclerosis, non-alcoholic fatty liver disease, diabetes and other ACSL3 related diseases. This article also further explores the role of ACSL3 in the process of lipid droplet synthesis, autophagy, and iron death.