title: Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains.
abstract: Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of "emerging" LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage.
authors.affiliation: Equip de Senyalització i Proliferació Cellular, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
authors.forename: Adam
authors.initials: A
authors.lastname: Kassan
authors.forename: Albert
authors.initials: A
authors.lastname: Herms
authors.forename: Andrea
authors.initials: A
authors.lastname: Fernández-Vidal
authors.forename: Marta
authors.initials: M
authors.lastname: Bosch
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Schieber
authors.forename: Babu J N
authors.initials: BJ
authors.lastname: Reddy
authors.forename: Alba
authors.initials: A
authors.lastname: Fajardo
authors.forename: Mariona
authors.initials: M
authors.lastname: Gelabert-Baldrich
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Albert
authors.initials: A
authors.lastname: Pol
mesh_terms: D000818:Animals; D019556:COS Cells; D051242:Caveolin 1 / Q000737:chemistry; D002522:Chlorocebus aethiops; D003066:Coenzyme A Ligases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000032:analysis; D042541:Intracellular Space; D050356:Lipid Metabolism; D008780:Methyltransferases / Q000737:chemistry; D015202:Protein Engineering; D021382:Protein Sorting Signals; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D051242:Caveolin 1; D021382:Protein Sorting Signals; D049452:Green Fluorescent Proteins; D008780:Methyltransferases; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase