Department of Molecular Cell Biology and Anatomy, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Nat Commun. 2019 Jan 28;10(1):473. doi: 10.1038/s41467-019-08411-x.
The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here we show that nuclear LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs, a precursor to very low-density lipoproprotein (VLDL) generated in the ER lumen by microsomal triglyceride transfer protein. ApoB-free lumenal LDs accumulate under ER stress, grow within the lumen of the type I nucleoplasmic reticulum, and turn into nucleoplasmic LDs by disintegration of the surrounding inner nuclear membrane. Oleic acid with or without tunicamycin significantly increases the formation of nucleoplasmic LDs, to which CDP-choline diacylglycerol phosphotransferase α (CCTα) is recruited, resulting in activation of phosphatidylcholine (PC) synthesis. Perilipin-3 competes with CCTα in binding to nucleoplasmic LDs, and thus, knockdown and overexpression of perilipin-3 increases and decreases PC synthesis, respectively. The results indicate that nucleoplasmic LDs in hepatocytes constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.
核内脂滴（LDs）的起源和生理意义尚不清楚。在这里，我们表明肝细胞中的核 LDs 来源于载脂蛋白 B（ApoB）-游离腔室 LDs，后者是内质网腔中由微粒体甘油三酯转移蛋白生成的极低密度脂蛋白（VLDL）的前体。ApoB-游离腔室 LDs 在 ER 应激下积累，在 I 型核质网的腔室内生长，并通过周围内核膜的解体转化为核质 LDs。油酸（有或没有衣霉素）显著增加核质 LDs 的形成，CDP-胆碱二酰甘油磷酸转移酶α（CCTα）被募集到核质 LDs 上，从而激活磷脂酰胆碱（PC）合成。 perilipin-3 与 CCTα 在结合核质 LDs 上竞争，因此，perilipin-3 的敲低和过表达分别增加和减少 PC 合成。结果表明，肝细胞中的核质 LDs 构成了一种反馈机制，根据 ER 应激来调节 PC 合成。
