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Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis

Author

Listed:
  • Kamil Sołtysik

    (Nagoya University Graduate School of Medicine)

  • Yuki Ohsaki

    (Nagoya University Graduate School of Medicine)

  • Tsuyako Tatematsu

    (Nagoya University Graduate School of Medicine)

  • Jinglei Cheng

    (Nagoya University Graduate School of Medicine)

  • Toyoshi Fujimoto

    (Nagoya University Graduate School of Medicine)

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 CTP:phosphocholine cytidylyltransferase 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.

Suggested Citation

  • Kamil Sołtysik & Yuki Ohsaki & Tsuyako Tatematsu & Jinglei Cheng & Toyoshi Fujimoto, 2019. "Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08411-x
    DOI: 10.1038/s41467-019-08411-x
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    Cited by:

    1. Keiji Kajiwara & Hiroshi Osaki & Steffen Greßies & Keiko Kuwata & Ju Hyun Kim & Tobias Gensch & Yoshikatsu Sato & Frank Glorius & Shigehiro Yamaguchi & Masayasu Taki, 2022. "A negative-solvatochromic fluorescent probe for visualizing intracellular distributions of fatty acid metabolites," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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