Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
J Cell Biol. 2012 Sep 3;198(5):895-911. doi: 10.1083/jcb.201201139. Epub 2012 Aug 27.
At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER-LD interaction and facilitate neutral lipid loading into LDs are poorly understood. In this paper, we present evidence that FATP1/acyl-CoA synthetase and DGAT2/diacylglycerol acyltransferase are components of a triglyceride synthesis complex that facilitates LD expansion. A loss of FATP1 or DGAT2 function blocked LD expansion in Caenorhabditis elegans. FATP1 preferentially associated with DGAT2, and they acted synergistically to promote LD expansion in mammalian cells. Live imaging indicated that FATP1 and DGAT2 are ER and LD resident proteins, respectively, and electron microscopy revealed FATP1 and DGAT2 foci close to the LD surface. Furthermore, DGAT2 that was retained in the ER failed to support LD expansion. We propose that the evolutionarily conserved FATP1-DGAT2 complex acts at the ER-LD interface and couples the synthesis and deposition of triglycerides into LDs both physically and functionally.
在亚细胞水平上，脂肪储存仅限于称为脂滴 (LDs) 的进化保守隔室，其与内质网 (ER) 密切相关。然而，允许 ER-LD 相互作用并促进中性脂质加载到 LD 中的分子机制尚不清楚。在本文中，我们提供了证据表明 FATP1/酰基辅酶 A 合成酶和 DGAT2/二酰基甘油酰基转移酶是促进 LD 扩张的甘油三酯合成复合物的组成部分。FATP1 或 DGAT2 功能丧失会阻止秀丽隐杆线虫中 LD 的扩张。FATP1 优先与 DGAT2 结合，它们协同作用促进哺乳动物细胞中 LD 的扩张。实时成像表明 FATP1 和 DGAT2 分别是 ER 和 LD 的驻留蛋白，电子显微镜显示 FATP1 和 DGAT2 焦点靠近 LD 表面。此外，保留在 ER 中的 DGAT2 无法支持 LD 扩张。我们提出，进化上保守的 FATP1-DGAT2 复合物在 ER-LD 界面处起作用，并在物理和功能上将甘油三酯的合成和沉积偶联到 LD 中。
