跨膜蛋白68调控三酰甘油合成和甘油磷脂代谢  

Transmembrane Protein 68 Regulates Triglyceride Synthesis and Glycerophospholipid Metabolism

作　　者：张春艳[1] 余庆[1] 逄慧敏 黄飞飞 常平安[1,2] ZHANG Chunyan;YU Qing;PANG Huimin;HUANG Feifei;CHANG Ping’an(School of Life Health Information,Chongqing University of Posts and Telecommunications,Chongqing 400065,China;Chongqing Key Laboratory of Big Data for Bio-intelligence,Chongqing 400065,China)

机构地区：[1]重庆邮电大学生命健康信息学院,中国重庆400065 [2]重庆市大数据生物智能重点实验室,中国重庆400065

出　　处：《生命科学研究》2025年第1期14-20,共7页Life Science Research

基　　金：重庆市自然科学基金项目(CSTB2022NSCQ-MSX0957);重庆市教委科技项目(KJQN20230065)。

摘　　要：作为一种二酰甘油酰基转移酶,跨膜蛋白68(transmembrane protein 68,TMEM68)介导一条不依赖酰基辅酶A:二酰甘油酰基转移酶(acyl-CoA:diacylglycerol acyltransferase,DGAT)的三酰甘油生物合成新途径。然而TMEM68催化三酰甘油合成的酰基供体尚不明确。本文通过比较超表达TMEM68对不同脂酰链饱和度的甘油酯、脂肪酸和甘油磷脂的作用,发现超表达TMEM68对不同饱和度的三酰甘油、二酰甘油、脂肪酸、磷脂酰胆碱和磷脂酰乙醇胺及其醚脂表现出不同的影响,并且这些脂质的变化存在一定的相关性;通过DGAT抑制剂处理,发现TMEM68不依赖DGAT活性合成三酰甘油,促进脂滴形成;通过分子对接分析,发现TMEM68与磷脂:二酰甘油酰基转移酶具有相似甚至更强的针对磷脂酰胆碱和磷脂酰乙醇胺及其醚脂的结合力。这些结果提示,TMEM68以二酰甘油为酰基受体,可能利用甘油磷脂作为酰基供体合成三酰甘油。As a diacylglycerol acyltransferase,transmembrane protein 68(TMEM68)mediates a novel pathway for triglyceride biosynthesis independent of acyl-CoA:diacylglycerol acyltransferase(DGAT).However,the acyl donor for TMEM68 to catalyze triacylglycerol synthesis has not been identified.In this paper,through comparing influences of TMEM68 overexpression on glycerolipids,fatty acids and glycerophospholipids with different acyl chain saturations,it was found that TMEM68 overexpression exerted different effects on triacylglycerol,diacylglycerol,fatty acids,phosphatidylcholine,phosphatidylethanolamine and their ether lipids with different saturations,and a certain correlation existed in alterations of these lipid metabolites.After DGAT inhibitor treatment,it was found that TMEM68 synthesized triacylglycerol and promoted lipid droplet formation without relying on DGAT activity.Moreover,through molecular docking analysis,TMEM68 proved to have similar or even stronger binding capacity to phosphatidylcholine,phosphatidylethanolamine and their ether lipids compared with phospholipid:diacylglycerol acyltransferase.These results together suggest that TMEM68 may use diacylglycerol as an acyl acceptor and glycerophospholipid as an acyl donor to synthesize triacylglycerol.

关 键 词：三酰甘油合成 甘油磷脂 二酰甘油 脂滴 跨膜蛋白68(TMEM68) 

分 类 号：Q26[生物学—细胞生物学] Q555