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

Florian Wilfling (1) , Abdou Rachid Thiam (2, 1) , Maria-Jesus Olarte (1) , Jing Wang (1) , Rainer Beck (3, 1) , Travis J. Gould (1) , Edward S. Allgeyer (1) , Frederic Pincet (1, 2) , Jörg Bewersdorf (1) , Robert V. Farese Jr. (4, 5) , Tobias C. Walther (1)

1 YSM - Yale School of Medicine [New Haven, Connecticut]
2 LPS - Laboratoire de Physique Statistique de l'ENS
3 Universität Heidelberg [Heidelberg] = Heidelberg University
4 Gladstone Institute of Cardiovascular Disease
5 UC San Francisco - University of California [San Francisco]

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.

Domaines: Sciences du Vivant [q-bio]

Florian Wilfling, Abdou Rachid Thiam, Maria-Jesus Olarte, Jing Wang, Rainer Beck, et al.. Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting. eLife, 2014, 3, pp.e01607. ⟨10.7554/eLife.01607⟩. ⟨hal-01316698⟩