title: An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.
abstract: Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Markgraf
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robin W
authors.initials: RW
authors.lastname: Klemm
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mirco
authors.initials: M
authors.lastname: Junker
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
authors.forename: Hans K
authors.initials: HK
authors.lastname: Hannibal-Bach
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
authors.forename: Christer S
authors.initials: CS
authors.lastname: Ejsing
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: tom_rapoport@hms.harvard.edu.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Rapoport
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: C500973:Ice2 protein, S cerevisiae; D008565:Membrane Proteins; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; C494880:DGA1 protein, S cerevisiae; D051048:Diacylglycerol O-Acyltransferase