title: The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix.
abstract: Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD-LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Barneda
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Joan
authors.initials: J
authors.lastname: Planas-Iglesias
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Gaspar
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Dariush
authors.identifier: http://orcid.org/0000-0002-0505-779X
authors.initials: D
authors.lastname: Mohammadyani
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, United Kingdom.
authors.forename: Sunil
authors.initials: S
authors.lastname: Prasannan
authors.affiliation: Microscopy Facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Dirk
authors.initials: D
authors.lastname: Dormann
authors.affiliation: Department of Food Science, Rutgers Center for Lipid Research, Rutgers University, New Brunswick, United States.
authors.forename: Gil-Soo
authors.initials: GS
authors.lastname: Han
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Jesch
authors.affiliation: Department of Food Science, Rutgers Center for Lipid Research, Rutgers University, New Brunswick, United States.
authors.forename: George M
authors.initials: GM
authors.lastname: Carman
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Valerian
authors.initials: V
authors.lastname: Kagan
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Parker
authors.affiliation: Signalling Programme, Babraham Institute, Cambridge, United Kingdom.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ktistakis
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.|Department of Bioengineering, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Judith
authors.initials: J
authors.lastname: Klein-Seetharaman
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, United Kingdom.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dixon
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Henry
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.|Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Christian
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D066292:Lipid Droplets / Q000378:metabolism*; D051379:Mice; D010712:Phosphatidic Acids / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D010712:Phosphatidic Acids
keywords: S. cerevisiae; biophysics; brown adipose tissue; cell biology; human; lipid Droplets; mouse; phospholipids; structural biology