1. Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner
- Author
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Asami Maeda, Jinglei Cheng, Toyoshi Fujimoto, Yuki Ohsaki, Kamil Sołtysik, Tsuyako Tatematsu, and Shin-ya Morita
- Subjects
Organelles ,Cell Nucleus ,Gene knockdown ,Nuclear Envelope ,Membrane and Lipid Biology ,Phosphatidic Acids ,Cell Biology ,Phosphatidic acid ,Lipid Droplets ,Biology ,Biochemistry ,Seipin ,Cell biology ,Cell nucleus ,chemistry.chemical_compound ,medicine.anatomical_structure ,Metabolism ,chemistry ,Cytoplasm ,Lipid droplet ,Report ,GTP-Binding Protein gamma Subunits ,medicine ,Inner membrane ,Intracellular - Abstract
Sołtysik et al. show that the inner nuclear membrane of nonhepatocytes harbors triglyceride synthesis enzymes and generates nuclear lipid droplets (LDs). Seipin knockdown increases nuclear LDs through upregulating lipin-1β transcription and increasing phosphatidic acid levels in the nucleus., Nuclear lipid droplets (LDs) in hepatocytes are derived from precursors of very-low-density lipoprotein in the ER lumen, but it is not known how cells lacking the lipoprotein secretory function form nuclear LDs. Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride synthesis enzymes, including ACSL3, AGPAT2, GPAT3/GPAT4, and DGAT1/DGAT2, and generates nuclear LDs in situ. mTOR inhibition increases nuclear LDs by inducing the nuclear translocation of lipin-1 phosphatidic acid (PA) phosphatase. Seipin, a protein essential for normal cytoplasmic LD formation in the ER, is absent in the INM. Knockdown of seipin increases nuclear LDs and PA in the nucleus, whereas seipin overexpression decreases these. Seipin knockdown also up-regulates lipin-1β expression, and lipin-1 knockdown decreases the effect of seipin knockdown on nuclear LDs without affecting PA redistribution. These results indicate that seipin is not directly involved in nuclear LD formation but instead restrains it by affecting lipin-1 expression and intracellular PA distribution.
- Published
- 2020