title: Protein Crowding Is a Determinant of Lipid Droplet Protein Composition.
abstract: Lipid droplets (LDs) are lipid storage organelles that grow or shrink, depending on the availability of metabolic energy. Proteins recruited to LDs mediate many metabolic functions, including phosphatidylcholine and triglyceride synthesis. How the LD protein composition is tuned to the supply and demand for lipids remains unclear. We show that LDs, in contrast to other organelles, have limited capacity for protein binding. Consequently, macromolecular crowding plays a major role in determining LD protein composition. During lipolysis, when LDs and their surfaces shrink, some, but not all, proteins become displaced. In vitro studies show that macromolecular crowding, rather than changes in monolayer lipid composition, causes proteins to fall off the LD surface. As predicted by a crowding model, proteins compete for binding to the surfaces of LDs. Moreover, the LD binding affinity determines protein localization during lipolysis. Our findings identify protein crowding as an important principle in determining LD protein composition.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Kory
authors.affiliation: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA; Laboratoire de Physique Statistique, École Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, 24 Rue Lhomond, 75005 Paris, France.
authors.forename: Abdou-Rachid
authors.initials: AR
authors.lastname: Thiam
authors.affiliation: Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: robert@hsph.harvard.edu.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
authors.affiliation: Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: twalther@hsph.harvard.edu.
authors.forename: Tobias C
authors.initials: TC
authors.lastname: Walther
mesh_terms: D000818:Animals; D002460:Cell Line; D019916:Choline-Phosphate Cytidylyltransferase / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D066292:Lipid Droplets / Q000737:chemistry*; D050356:Lipid Metabolism; D008066:Lipolysis; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D005992:Glycerol-3-Phosphate O-Acyltransferase; C481021:Cct1protein, Drosophila; D019916:Choline-Phosphate Cytidylyltransferase