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      Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites

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          Abstract

          The lipid droplet–associated protein Fsp27 mediates lipid droplet growth by promoting directional lipid transfer from smaller to larger lipid droplets.

          Abstract

          Lipid droplets (LDs) are dynamic cellular organelles that control many biological processes. However, molecular components determining LD growth are poorly understood. Genetic analysis has indicated that Fsp27, an LD-associated protein, is important in controlling LD size and lipid storage in adipocytes. In this paper, we demonstrate that Fsp27 is focally enriched at the LD–LD contacting site (LDCS). Photobleaching revealed the occurrence of lipid exchange between contacted LDs in wild-type adipocytes and Fsp27-overexpressing cells but not Fsp27-deficient adipocytes. Furthermore, live-cell imaging revealed a unique Fsp27-mediated LD growth process involving a directional net lipid transfer from the smaller to larger LDs at LDCSs, which is in accordance with the biophysical analysis of the internal pressure difference between the contacting LD pair. Thus, we have uncovered a novel molecular mechanism of LD growth mediated by Fsp27.

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          Most cited references 27

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          Lipid droplets: a unified view of a dynamic organelle.

          Lipid droplets form the main lipid store in eukaryotic cells. Although all cells seem to be able to generate lipid droplets, their biogenesis, regulatory mechanisms and interactions with other organelles remain largely elusive. In this article, we outline some of the recent developments in lipid droplet cell biology. We show the mobile and dynamic nature of this organelle, and advocate the adoption of a unified nomenclature to consolidate terminology in this emerging field.
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            Lipid droplets finally get a little R-E-S-P-E-C-T.

            Long underappreciated as important cellular organelles, lipid droplets are finally being recognized as dynamic structures with a complex and interesting biology. In light of this newfound respect, we discuss emerging views on lipid droplet biology and speculate on the major advances to come.
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              Functional genomic screen reveals genes involved in lipid-droplet formation and utilization.

              Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets enclosed in a monolayer of phospholipids and associated proteins. These dynamic organelles serve as the principal reservoirs for storing cellular energy and for the building blocks for membrane lipids. Excessive lipid accumulation in cells is a central feature of obesity, diabetes and atherosclerosis, yet remarkably little is known about lipid-droplet cell biology. Here we show, by means of a genome-wide RNA interference (RNAi) screen in Drosophila S2 cells that about 1.5% of all genes function in lipid-droplet formation and regulation. The phenotypes of the gene knockdowns sorted into five distinct phenotypic classes. Genes encoding enzymes of phospholipid biosynthesis proved to be determinants of lipid-droplet size and number, suggesting that the phospholipid composition of the monolayer profoundly affects droplet morphology and lipid utilization. A subset of the Arf1-COPI vesicular transport proteins also regulated droplet morphology and lipid utilization, thereby identifying a previously unrecognized function for this machinery. These phenotypes are conserved in mammalian cells, suggesting that insights from these studies are likely to be central to our understanding of human diseases involving excessive lipid storage.
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                12 December 2011
                : 195
                : 6
                : 953-963
                Affiliations
                [1 ]Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing 100084, China
                [2 ]Institute for Molecular Bioscience and [3 ]Centre for Microscopy and Microanalysis, University of Queensland, Brisbane 4072, Australia
                [4 ]Life Sciences Institute, National University of Singapore, Queenstown, Singapore 119077
                [5 ]School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052, Australia
                Author notes
                Correspondence to Peng Li: li-peng@ 123456mail.tsinghua.edu.cn

                J. Gong and Z. Sun contributed equally to this paper.

                Article
                201104142
                10.1083/jcb.201104142
                3241734
                22144693
                © 2011 Gong et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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