Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting.
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.
Department of Cell Biology, Yale University School of Medicine, New Haven, United States.
Florian
F
Wilfling
Abdou Rachid
AR
Thiam
Maria-Jesus
MJ
Olarte
Jing
J
Wang
Rainer
R
Beck
Travis J
TJ
Gould
Edward S
ES
Allgeyer
Frederic
F
Pincet
Jörg
J
Bewersdorf
Robert V
RV
Farese
Tobias C
TC
Walther
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D022181:COP-Coated Vesicles / Q000378:metabolism*; D002460:Cell Line; D020755:Coat Protein Complex I / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism; D034622:RNA Interference; D013500:Surface Tension; D013997:Time Factors; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism
D020755:Coat Protein Complex I; D029721:Drosophila Proteins; D010743:Phospholipids; D014280:Triglycerides; D008049:Lipase; C559670:BMM protein, Drosophila; D020823:ADP-Ribosylation Factor 1
ER-lipid droplet connections; lipid droplet; lipolysis; protein targeting; triglyceride synthesis