PML isoform II plays a critical role in nuclear lipid droplet formation

J Cell Biol. 2016 Jan 4;212(1):29-38. doi: 10.1083/jcb.201507122.

Abstract

Lipid droplets (LDs) in the nucleus of hepatocyte-derived cell lines were found to be associated with premyelocytic leukemia (PML) nuclear bodies (NBs) and type I nucleoplasmic reticulum (NR) or the extension of the inner nuclear membrane. Knockdown of PML isoform II (PML-II) caused a significant decrease in both nuclear LDs and type I NR, whereas overexpression of PML-II increased both. Notably, these effects were evident only in limited types of cells, in which a moderate number of nuclear LDs exist intrinsically, and PML-II was targeted not only at PML NBs, but also at the nuclear envelope, excluding lamins and SUN proteins. Knockdown of SUN proteins induced a significant increase in the type I NR and nuclear LDs, but these effects were cancelled by simultaneous knockdown of PML-II. Nuclear LDs harbored diacylglycerol O-acyltransferase 2 and CTP:phosphocholine cytidylyltransferase α and incorporated newly synthesized lipid esters. These results corroborated that PML-II plays a critical role in generating nuclear LDs in specific cell types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Female
  • Humans
  • Lipid Droplets / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Nuclear Proteins / metabolism*
  • Promyelocytic Leukemia Protein
  • Protein Isoforms / metabolism
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Protein Isoforms
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human

Associated data

  • RefSeq/NM_001122