title: Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets.
abstract: Lipid droplets (LDs) store metabolic energy and membrane lipid precursors. With excess metabolic energy, cells synthesize triacylglycerol (TG) and form LDs that grow dramatically. It is unclear how TG synthesis relates to LD formation and growth. Here, we identify two LD subpopulations: smaller LDs of relatively constant size, and LDs that grow larger. The latter population contains isoenzymes for each step of TG synthesis. Glycerol-3-phosphate acyltransferase 4 (GPAT4), which catalyzes the first and rate-limiting step, relocalizes from the endoplasmic reticulum (ER) to a subset of forming LDs, where it becomes stably associated. ER-to-LD targeting of GPAT4 and other LD-localized TG synthesis isozymes is required for LD growth. Key features of GPAT4 ER-to-LD targeting and function in LD growth are conserved between Drosophila and mammalian cells. Our results explain how TG synthesis is coupled with LD growth and identify two distinct LD subpopulations based on their capacity for localized TG synthesis.
authors: Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA.
authors: Florian
authors: F
authors: Wilfling
authors: Huajin
authors: H
authors: Wang
authors: Joel T
authors: JT
authors: Haas
authors: Natalie
authors: N
authors: Krahmer
authors: Travis J
authors: TJ
authors: Gould
authors: Aki
authors: A
authors: Uchida
authors: Ji-Xin
authors: JX
authors: Cheng
authors: Morven
authors: M
authors: Graham
authors: Romain
authors: R
authors: Christiano
authors: Florian
authors: F
authors: Fröhlich
authors: Xinran
authors: X
authors: Liu
authors: Kimberly K
authors: KK
authors: Buhman
authors: Rosalind A
authors: RA
authors: Coleman
authors: Joerg
authors: J
authors: Bewersdorf
authors: Robert V
authors: RV
authors: Farese
authors: Tobias C
authors: TC
authors: Walther
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D008055:Lipids; D010743:Phospholipids; D014280:Triglycerides; C529425:GPAT4 protein, mouse; D005992:Glycerol-3-Phosphate O-Acyltransferase; C516957:DGAT2 protein, mouse; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase