Arf1/COPI machinery acts directly on lipid droplets and enables their connection to the ER for protein targeting
Florian Wilfling,
Abdou Rachid Thiam,
Maria-Jesus Olarte,
Jing Wang,
Rainer Beck,
Travis J Gould,
Edward S Allgeyer,
Frederic Pincet,
Jörg Bewersdorf,
Robert V Farese Jr,
Tobias C Walther
Affiliations
Florian Wilfling
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Abdou Rachid Thiam
Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Laboratoire de Physique Statistique UMR 8550, Ecole Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, Paris, France
Maria-Jesus Olarte
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Jing Wang
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Rainer Beck
Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Heidelberg University Biochemistry Centre, University of Heidelberg, Heidelberg, Germany
Travis J Gould
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Edward S Allgeyer
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Frederic Pincet
Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Laboratoire de Physique Statistique UMR 8550, Ecole Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, Paris, France
Jörg Bewersdorf
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
Robert V Farese Jr
Gladstone Institute of Cardiovascular Disease, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United States; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
Tobias C Walther
Department of Cell Biology, Yale University School of Medicine, New Haven, United States
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.