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Elife. 2016 Aug 26;5. pii: e16582. doi: 10.7554/eLife.16582.

Seipin is required for converting nascent to mature lipid droplets.

Author information

1
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States.
2
Department of Genetics and Complex Diseases, Harvard T H Chan School of Public Health, Boston, United States.
3
Department of Cell Biology, Harvard Medical School, Boston, United States.
4
Department of Genetics, Harvard Medical School, Boston, United States.
5
Center for Cellular and Molecular Imaging, Department of Cell Biology, Yale School of Medicine, New Haven, United States.
6
Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Univ Paris 06, CNRS UMR 8550, Paris, France.
7
The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom.
8
Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, United States.
9
Molecular Membrane Biology Section, Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany.
10
VILLUM Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
11
Department of Pediatrics, Harvard Medical School, Boston, United States.
12
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States.
13
Howard Hughes Medical Institute, Boston, United States.
14
Broad Institute of Harvard and MIT, Cambridge, United States.

Abstract

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.

KEYWORDS:

D. melanogaster; LiveDrop; cell biology; endoplasmic reticulum; human; lipid droplet; lipid metabolism; organelle biogenesis; seipin

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