title: Targeting Fat: Mechanisms of Protein Localization to Lipid Droplets.
abstract: How proteins specifically localize to the phospholipid monolayer surface of lipid droplets (LDs) is being unraveled. We review here the major known pathways of protein targeting to LDs and suggest a classification framework based on the localization origin for the protein. Class I proteins often have a membrane-embedded, hydrophobic 'hairpin' motif, and access LDs from the endoplasmic reticulum (ER) either during LD formation or after formation via ER-LD membrane bridges. Class II proteins access the LD surface from the cytosol and bind through amphipathic helices or other hydrophobic domains. Other proteins require lipid modifications or protein-protein interactions to bind to LDs. We summarize knowledge for targeting and removal of the different classes, and highlight areas needing investigation.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Kory
authors.affiliation: Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, 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, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute (HHMI), Boston, MA, USA. Electronic address: twalther@hsph.harvard.edu.
authors.forename: Tobias C
authors.initials: TC
authors.lastname: Walther
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism* / Q000648:ultrastructure; D008954:Models, Biological; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: amphipathic α-helix; hydrophobic hairpin; lipolysis; organelle protein composition; triglyceride storage