Choudhary Vineet, Schneiter Roger
All India Institute of Medical Sciences (AIIMS), Department of Biotechnology, New Delhi, 110029, India.
University of Fribourg, Department of Biology, 1700 Fribourg, Switzerland.
Microb Cell. 2020 Jun 16;7(8):218-221. doi: 10.15698/mic2020.08.727.
Lipid droplets (LDs) are cellular compartments dedicated to the storage of metabolic energy in the form of neutral lipids, commonly known as "fat". The biogenesis of LDs takes place in the endoplasmic reticulum (ER), but its spatial and temporal organization is poorly understood. How exactly sites of LD formation are selected and the succession of proteins and lipids needed to mediate this process remains to be defined. In our current study we show that the yeast triacylglycerol (TAG)-synthases, Lro1 and Dga1 get recruited to discrete ER subdomains where they initiate TAG synthesis and hence LD formation (Choudhary (2020), J Cell Biol). These ER subdomains are defined by yeast seipin, Fld1, and a regulator of diacylglycerol (DAG) production, Nem1. Both Fld1 and Nem1 are ER proteins which localize at contact sites between the ER and LDs. Interestingly, even in cells lacking LDs, Fld1 and Nem1 show punctate localization at ER subdomains independently of each other, but they are required together to recruit the TAG-synthases and hence create functional sites of LD biogenesis. Fld1/Nem1-containing ER subdomains recruit additional LD biogenesis factors, such as Yft2, Pex30, Pet10 and Erg6, and these membrane domains become enriched in DAG. In conclusion, Fld1 and Nem1 play a crucial role in defining ER subdomains for the recruitment of proteins and lipids needed to initiate LD biogenesis.
脂滴（LDs）是细胞内专门用于以中性脂质形式储存代谢能量的区室，中性脂质通常被称为“脂肪”。脂滴的生物发生在内质网（ER）中进行，但其时空组织仍知之甚少。究竟如何选择脂滴形成位点以及介导这一过程所需的蛋白质和脂质的相继作用仍有待确定。在我们当前的研究中，我们表明酵母三酰甘油（TAG）合成酶Lro1和Dga1被招募到离散的内质网亚结构域，在那里它们启动TAG合成，从而引发脂滴形成（乔杜里（2020年），《细胞生物学杂志》）。这些内质网亚结构域由酵母seipin、Fld1和二酰甘油（DAG）产生的调节因子Nem1所界定。Fld1和Nem1都是内质网蛋白，它们定位于内质网与脂滴之间的接触位点。有趣的是，即使在缺乏脂滴的细胞中，Fld1和Nem1也彼此独立地在内质网亚结构域呈现点状定位，但它们共同作用才能招募TAG合成酶，从而创建脂滴生物发生的功能位点。含有Fld1/Nem1的内质网亚结构域招募其他脂滴生物发生因子，如Yft2、Pex30、Pet10和Erg6，并且这些膜结构域富含DAG。总之，Fld1和Nem1在界定内质网亚结构域以招募启动脂滴生物发生所需的蛋白质和脂质方面发挥着关键作用。
