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Elife. 2015 Nov 26;4:e07485. doi: 10.7554/eLife.07485.

The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix.

Author information

1
Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
2
Warwick Medical School, University of Warwick, Coventry, United Kingdom.
3
Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
4
Department of Bioengineering, University of Pittsburgh, Pittsburgh, United States.
5
Department of Chemistry, University of Warwick, Coventry, United Kingdom.
6
Microscopy Facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
7
Department of Food Science, Rutgers Center for Lipid Research, Rutgers University, New Brunswick, United States.
8
Signalling Programme, Babraham Institute, Cambridge, United Kingdom.

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.

KEYWORDS:

S. cerevisiae; biophysics; brown adipose tissue; cell biology; human; lipid Droplets; mouse; phospholipids; structural biology

PMID:
26609809
PMCID:
PMC4755750
DOI:
10.7554/eLife.07485
[Indexed for MEDLINE]
Free PMC Article

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