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- Title
Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis.
- Authors
Sołtysik, Kamil; Ohsaki, Yuki; Tatematsu, Tsuyako; Cheng, Jinglei; Fujimoto, Toyoshi
- Abstract
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. The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here authors show that nucleoplasmic LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs and constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-08411-x