TY - JOUR
T1 - The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix
AU - Barneda, David
AU - Planas-Iglesias, Joan
AU - Gaspar, Maria L.
AU - Mohammadyani, Dariush
AU - Prasannan, Sunil
AU - Dormann, Dirk
AU - Han, Gil Soo
AU - Jesch, Stephen A.
AU - Carman, George M.
AU - Kagan, Valerian
AU - Parker, Malcolm G.
AU - Ktistakis, Nicholas T.
AU - Klein-Seetharaman, Judith
AU - Dixon, Ann M.
AU - Henry, Susan A.
AU - Christian, Mark
N1 - Publisher Copyright:
© Barneda et al.
PY - 2015/11/26
Y1 - 2015/11/26
N2 - 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.
AB - 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.
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U2 - 10.7554/eLife.07485
DO - 10.7554/eLife.07485
M3 - Article
C2 - 26609809
AN - SCOPUS:84957922839
SN - 2050-084X
VL - 4
JO - eLife
JF - eLife
IS - NOVEMBER2015
M1 - e07485
ER -