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.
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4 January 2021
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December 14 2020
Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner
Kamil Sołtysik,
Kamil Sołtysik
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Yuki Ohsaki,
Yuki Ohsaki
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Tsuyako Tatematsu,
Tsuyako Tatematsu
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Jinglei Cheng,
Jinglei Cheng
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Asami Maeda,
Asami Maeda
2
Laboratory of Molecular Cell Biology, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan
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Shin-ya Morita,
Shin-ya Morita
3
Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu City, Shiga, Japan
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Toyoshi Fujimoto
2
Laboratory of Molecular Cell Biology, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan
Correspondence to Toyoshi Fujimoto: t.fujimoto.xl@juntendo.ac.jp
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Kamil Sołtysik
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Yuki Ohsaki
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Tsuyako Tatematsu
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Jinglei Cheng
1
Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Asami Maeda
2
Laboratory of Molecular Cell Biology, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan
Shin-ya Morita
3
Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu City, Shiga, Japan
Toyoshi Fujimoto
2
Laboratory of Molecular Cell Biology, Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan
Correspondence to Toyoshi Fujimoto: t.fujimoto.xl@juntendo.ac.jp
Received:
May 13 2020
Revision Received:
September 25 2020
Accepted:
November 11 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Japan Society for the Promotion of Science
(18K06829, 15H05902, 18H04023)
© 2020 Sołtysik et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (1): e202005026.
Article history
Received:
May 13 2020
Revision Received:
September 25 2020
Accepted:
November 11 2020
Connected Content
Citation
Kamil Sołtysik, Yuki Ohsaki, Tsuyako Tatematsu, Jinglei Cheng, Asami Maeda, Shin-ya Morita, Toyoshi Fujimoto; Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner. J Cell Biol 4 January 2021; 220 (1): e202005026. doi: https://doi.org/10.1083/jcb.202005026
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