title: PML isoform II plays a critical role in nuclear lipid droplet formation.
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.
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohsaki
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yukichika
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Jinglei
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Jokitalo
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan tfujimot@med.nagoya-u.ac.jp.
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human