title: COPI complex is a regulator of lipid homeostasis.
abstract: Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.
authors.affiliation: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. mbeller@gwdg.de
authors.forename: Mathias
authors.initials: M
authors.lastname: Beller
authors.forename: Carole
authors.initials: C
authors.lastname: Sztalryd
authors.forename: Noel
authors.initials: N
authors.lastname: Southall
authors.forename: Ming
authors.initials: M
authors.lastname: Bell
authors.forename: Herbert
authors.initials: H
authors.lastname: Jäckle
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Auld
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D020755:Coat Protein Complex I / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005216:Fat Body / Q000737:chemistry / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D000070778:Perilipin-1; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D020543:Proteome; D034622:RNA Interference
chemical_list: D002352:Carrier Proteins; D020755:Coat Protein Complex I; D029721:Drosophila Proteins; D005230:Fatty Acids, Nonesterified; D000070778:Perilipin-1; D010750:Phosphoproteins; D020543:Proteome