title: The FATP1-DGAT2 complex facilitates lipid droplet expansion at the ER-lipid droplet interface.
abstract: At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER-LD interaction and facilitate neutral lipid loading into LDs are poorly understood. In this paper, we present evidence that FATP1/acyl-CoA synthetase and DGAT2/diacylglycerol acyltransferase are components of a triglyceride synthesis complex that facilitates LD expansion. A loss of FATP1 or DGAT2 function blocked LD expansion in Caenorhabditis elegans. FATP1 preferentially associated with DGAT2, and they acted synergistically to promote LD expansion in mammalian cells. Live imaging indicated that FATP1 and DGAT2 are ER and LD resident proteins, respectively, and electron microscopy revealed FATP1 and DGAT2 foci close to the LD surface. Furthermore, DGAT2 that was retained in the ER failed to support LD expansion. We propose that the evolutionarily conserved FATP1-DGAT2 complex acts at the ER-LD interface and couples the synthesis and deposition of triglycerides into LDs both physically and functionally.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Ningyi
authors.initials: N
authors.lastname: Xu
authors.forename: Shaobing O
authors.initials: SO
authors.lastname: Zhang
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cole
authors.forename: Sean A
authors.initials: SA
authors.lastname: McKinney
authors.forename: Fengli
authors.initials: F
authors.lastname: Guo
authors.forename: Joel T
authors.initials: JT
authors.lastname: Haas
authors.forename: Sudheer
authors.initials: S
authors.lastname: Bobba
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
authors.forename: Ho Yi
authors.initials: HY
authors.lastname: Mak
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D050612:Fatty Acid Transport Proteins; D014280:Triglycerides; D051048:Diacylglycerol O-Acyltransferase