A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size

Cell Rep. 2013 May 30;3(5):1465-75. doi: 10.1016/j.celrep.2013.04.015. Epub 2013 May 16.

Abstract

Lipid droplets (LDs) are the major fat storage organelles in eukaryotic cells, but how their size is regulated is unknown. Using genetic screens in C. elegans for LD morphology defects in intestinal cells, we found that mutations in atlastin, a GTPase required for homotypic fusion of endoplasmic reticulum (ER) membranes, cause not only ER morphology defects, but also a reduction in LD size. Similar results were obtained after depletion of atlastin or expression of a dominant-negative mutant, whereas overexpression of atlastin had the opposite effect. Atlastin depletion in Drosophila fat bodies also reduced LD size and decreased triglycerides in whole animals, sensitizing them to starvation. In mammalian cells, co-overexpression of atlastin-1 and REEP1, a paralog of the ER tubule-shaping protein DP1/REEP5, generates large LDs. The effect of atlastin-1 on LD size correlates with its activity to promote membrane fusion in vitro. Our results indicate that atlastin-mediated fusion of ER membranes is important for LD size regulation.

Publication types

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

MeSH terms

  • Animals
  • COS Cells
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chlorocebus aethiops
  • Cytoplasmic Vesicles / chemistry*
  • Cytoplasmic Vesicles / metabolism
  • Drosophila / metabolism
  • Endoplasmic Reticulum / metabolism
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mutation
  • RNA Interference
  • RNA, Small Interfering / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • REEP1 protein, human
  • RNA, Small Interfering
  • ATL1 protein, human
  • GTP Phosphohydrolases
  • GTP-Binding Proteins