Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting

Elife. 2014:3:e01607. doi: 10.7554/eLife.01607. Epub 2014 Feb 4.

Abstract

Lipid droplets (LDs) are ubiquitous organelles that store neutral lipids, such as triacylglycerol (TG), as reservoirs of metabolic energy and membrane precursors. The Arf1/COPI protein machinery, known for its role in vesicle trafficking, regulates LD morphology, targeting of specific proteins to LDs and lipolysis through unclear mechanisms. Recent evidence shows that Arf1/COPI can bud nano-LDs (∼60 nm diameter) from phospholipid-covered oil/water interfaces in vitro. We show that Arf1/COPI proteins localize to cellular LDs, are sufficient to bud nano-LDs from cellular LDs, and are required for targeting specific TG-synthesis enzymes to LD surfaces. Cells lacking Arf1/COPI function have increased amounts of phospholipids on LDs, resulting in decreased LD surface tension and impairment to form bridges to the ER. Our findings uncover a function for Arf1/COPI proteins at LDs and suggest a model in which Arf1/COPI machinery acts to control ER-LD connections for localization of key enzymes of TG storage and catabolism. DOI: http://dx.doi.org/10.7554/eLife.01607.001.

Keywords: ER-lipid droplet connections; lipid droplet; lipolysis; protein targeting; triglyceride synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • ADP-Ribosylation Factor 1 / genetics
  • ADP-Ribosylation Factor 1 / metabolism*
  • Animals
  • Biological Transport
  • COP-Coated Vesicles / metabolism*
  • Cell Line
  • Coat Protein Complex I / genetics
  • Coat Protein Complex I / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Lipase / genetics
  • Lipase / metabolism
  • Lipid Droplets / metabolism*
  • Lipolysis
  • Mice
  • Nanoparticles
  • Particle Size
  • Phospholipids / metabolism
  • RNA Interference
  • Surface Tension
  • Time Factors
  • Transfection
  • Triglycerides / metabolism

Substances

  • Coat Protein Complex I
  • Drosophila Proteins
  • Phospholipids
  • Triglycerides
  • Lipase
  • BMM protein, Drosophila
  • ADP-Ribosylation Factor 1