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Running 'LAPS' Around nLD: Nuclear Lipid Droplet Form and Function.

Michael J McPhee1, Jayme Salsman2, Jason Foster1

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Frontiers in Cell and Developmental Biology
|February 18, 2022
PubMed
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Nuclear lipid droplets (nLDs) and lipid-associated PML structures (LAPS) form in response to excess fatty acids, regulating nuclear lipid metabolism and stress responses.

Keywords:
CCTalphaPMLfatty acidlipinnuclear lipid dropletsphosphatidylcholine

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Lipid Metabolism

Background:

  • The nucleus contains various subdomains and condensates regulating chromatin, gene expression, and genomic stress.
  • Nuclear lipid droplets (nLDs) are novel subdomains formed upon cellular exposure to excess fatty acids.
  • nLDs resemble cytoplasmic lipid droplets but have distinct biogenesis involving nucleoplasmic reticulum and de novo lipid synthesis.

Purpose of the Study:

  • To review the current understanding of nuclear lipid droplet (nLD) and lipid-associated PML structure (LAPS) biogenesis.
  • To describe the structure and composition of nLDs and LAPS in relation to other PML-associated nuclear structures.
  • To elucidate the role of nLDs and LAPS in coordinating nuclear responses to fatty acid overload.

Main Methods:

  • Review of existing literature on nuclear lipid droplet and LAPS formation and function.
  • Analysis of nLD and LAPS structure, composition, and biogenesis mechanisms.
  • Comparison of nLDs/LAPS with canonical PML nuclear bodies (NBs).

Main Results:

  • nLDs emerge from the nucleoplasmic reticulum and are enriched with promyelocytic leukemia (PML) protein at the inner nuclear membrane.
  • Lipid-associated PML structures (LAPS) are nLDs retaining PML on their surface, distinct from canonical PML NBs.
  • Both nLDs and LAPS possess lipid biosynthetic enzymes, suggesting active roles in nuclear lipid synthesis and regulation.

Conclusions:

  • nLDs and LAPS are key players in the nuclear response to lipid stress, potentially regulating lipid metabolism and signaling.
  • The recruitment and retention of PML protein by nLDs to form LAPS may be crucial for managing fatty acid overload.
  • Further research into nLD and LAPS biogenesis and function is needed to fully understand their role in nuclear lipid homeostasis.