Lipid droplet and peroxisome biogenesis occur at the same ER subdomains

Nat Commun. 2018 Jul 27;9(1):2940. doi: 10.1038/s41467-018-05277-3.

Abstract

Nascent lipid droplet (LD) formation occurs in the endoplasmic reticulum (ER) membrane but it is not known how sites of biogenesis are determined. We previously identified ER domains in S. cerevisiae containing the reticulon homology domain (RHD) protein Pex30 that are regions where preperoxisomal vesicles (PPVs) form. Here, we show that Pex30 domains are also sites where most nascent LDs form. Mature LDs usually remain associated with Pex30 subdomains, and the same Pex30 subdomain can simultaneously associate with a LD and a PPV or peroxisome. We find that in higher eukaryotes multiple C2 domain containing transmembrane protein (MCTP2) is similar to Pex30: it contains an RHD and resides in ER domains where most nascent LD biogenesis occurs and that often associate with peroxisomes. Together, these findings indicate that most LDs and PPVs form and remain associated with conserved ER subdomains, and suggest a link between LD and peroxisome biogenesis.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Diacylglycerol O-Acyltransferase / metabolism
  • Endoplasmic Reticulum / metabolism*
  • GTP-Binding Protein gamma Subunits / genetics
  • GTP-Binding Protein gamma Subunits / metabolism
  • Gene Deletion
  • HeLa Cells
  • Humans
  • Lipid Droplets / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Methyltransferases / metabolism
  • Mutation
  • Organelle Biogenesis*
  • Peroxisomes / metabolism*
  • Protein Domains
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • GTP-Binding Protein gamma Subunits
  • MCTP2 protein, human
  • Membrane Proteins
  • Membrane Transport Proteins
  • Pex30 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • seipin protein, S cerevisiae
  • Methyltransferases
  • delta 24-sterol methyltransferase
  • DGA1 protein, S cerevisiae
  • Diacylglycerol O-Acyltransferase