Lipid droplets at aglanceYi Guo1,*, Kimberly R. Cordes1,Robert V. Farese, Jr1,2,3 andTobias C. Walther4

1Gladstone Institute of Cardiovascular Disease,1650 Owens Street, San Francisco, CA 94158,USA2Department of Biochemistry and Biophysics, and3Department of Medicine, University of California,600 16th Street, San Francisco, CA 94158, USA4Organelle Architecture and Dynamics, Max-PlanckInstitute of Biochemistry, Am Klopferspitz 18,D-82152 Martinsried, Germany*Author for correspondence(e-mail: yguo@gladstone.ucsf.edu)

Journal of Cell Science 122, 749-752Published by The Company of Biologists 2009doi:10.1242/jcs.037630

Lipid droplets (LDs) are the majorcellular organelles for the storage ofneutral lipids. Excessive lipid storage inLDs is central to the pathogenesis of

prevalent metabolic diseases, such asobesity, diabetes and atherosclerosis; LDsare, therefore, crucial in the developmentof these diseases. Long considered to beinert, LDs have recently attracted greatinterest as dynamic structures at the hubof lipid and energy metabolism. Majorfindings that highlight the diversityand dynamics of LDs include theidentification of key proteins that areinvolved in LD biology, the discovery ofdifferences in protein and lipidcompositions of LDs in different celltypes and physiological states, and thedemonstration of interactions betweenLDs and other organelles [e.g.peroxisomes, endosomes, endoplasmicreticulum (ER), plasma membrane andmitochondria].

Despite the acceleration of progress in LDresearch and in determining the many linksof LDs with prominent diseases, most

fundamental questions are not yet resolved.How and where are LDs formed? How areproteins and lipids recruited to LDs? Howdo they interact with other organelles?How are their number, size and distributionregulated? In addition, new and unexpectedconnections with other cellular processesand pathologies are being found. Examplesinclude the discovery that LDs play a rolein histone storage in early Drosophilamelanogaster development, and that LDsare required for efficient replication ofintracellular pathogens, such as Chlamydiatrachomatis and hepatitis C virus. Furtherresearch into LDs has also been sparked bythe increased interest in biofuels; becausethese are mainly oils that are stored in LDs,efforts to manipulate systems to store moretriglycerides in these organelles are alsolikely to benefit from a better understandingof the basic biology of fat storage. Theseand other questions pose many fascinatingbiological problems to be solved.

749Cell Science at a Glance

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β-adrenergicreceptor

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Lipid droplets

Lipid Droplets at a GlanceYi Guo, Kimberly R. Cordes, Robert V. Farese, Jr and Tobias C. Walther

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© Journal of Cell Science 2009 (122, pp. 749-752)

Abbreviations: ACAT, acyl-CoA:cholesterol acyltransferase; ACBP, acyl-CoA binding protein; ACC, acetyl CoA carboxylase; ACS, acyl-CoA synthetase; AGPAT, sn-1-acylglycerol-3-phosphate acyltransferase; ApoB, apolipoprotein B; ATGL, adipose tissue triacylglycerol lipase; cAMP, cyclic adenosine monophosphate; CGI-58, comparative gene identification-58; CM, chylomicron; CoA, coenzyme A; COPI, coatomer protein complex I; CPT, cholinephosphotransferase; CPTI, carnitine/acylcarnitine translocase I; DAG, diacylglycerol; DGAT, acyl-CoA:diacylglycerol acyltransferase; ER, endoplasmic reticulum; FA, fatty acid; FABP, fatty acid binding protein; FAS, fatty acid synthase; FAT (CD36), fatty acid translocase; FATP, fatty acid transport protein;

G3P, glycerol-3-phosphate; GPAT, glycerol-3-phosphate acyltransferase; HCV, hepatitis C virus; HSL, hormone-sensitive lipase; LDL, low density lipoprotein; LPA, lysophosphatidate; LPL, lipoprotein lipase; MAG, monoacylglycerol; MGAT, acyl-CoA:monoacylglycerol acyltransferase; MGL, monoacylglycerol lipase; MT, microtubule; NHR, nuclear hormone receptor; NLSE, neutral lipid synthesis enzyme; PA, phosphatidate; PAP, phosphatidic acid phosphohydrolase; PC, phosphatidylcholine; PERI, perilipin; PKA, protein kinase A; Rab, Ras-related protein; SE, sterol ester; SNARE, soluble N-ethylmaleimide-sensitive factor adaptor protein receptor; TAG, triacylglycerol; TNFα, tumor necrosis factor α; VLDL, very low density lipoprotein.

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This article highlights emerging topics inLD biology and summarizes our currentunderstanding of LD cellular functions. Inthe accompanying poster, the architectureof LDs is explained, and the biochemicalpathways leading to fat storage areillustrated in a cellular context. In addition,we portray current models for LDformation and highlight the interactions ofLDs with other organelles.

Lipid-droplet compositionLDs consist of an organic core comprisingneutral lipids (mainly triacylglycerols andsterol esters) that is bounded by amonolayer of phospholipids (Bartz et al.,2007a). This structure provides a uniqueseparation of the aqueous and organicphases of the cell. Several types of proteinsdecorate LDs (Bartz et al., 2007b; Brown,2001), including structural proteins(e.g. proteins of the perilipin family)(Brasaemle, 2007), lipid-synthesisenzymes [e.g. acetyl coenzyme A (CoA)carboxylase, acyl-CoA synthetase andacyl-CoA:diacylglycerol acyltransferase 2(DGAT2)] (Kuerschner et al., 2008; Stoneet al., 2009), lipases [e.g. adipose tissuetriacylglycerol lipase (ATGL)] andmembrane-trafficking proteins (e.g. Rab5,Rab18 and ARF1). Adding to thecomplexity, different LDs in a cell cancontain different proteins (Ducharme andBickel, 2008) and have different rates ofacquiring triacylglycerol (Kuerschneret al., 2008). This suggests that cellscontain distinct types of LDs withspecialized functions.

Considering the composition of LDs, it isnot well understood how proteins target toLDs and how this localization is regulated.Conceptually, proteins that containtransmembrane-spanning domains withhydrophilic domains on either side of amembrane bilayer cannot target to themonolayer surface of an LD; instead, thereare at least two probable alternativemechanisms. First, proteins might use longmembrane-embedded domains that enterand exit the membrane on the same side ofthe lipid monolayer. This mechanism waspostulated for caveolins, which target tospecialized domains of the plasmamembrane and LDs (Martin and Parton,2006), and for the lipid-synthesis enzymeDGAT2 (Kuerschner et al., 2008; Stoneet al., 2006). Second, proteins might bindLD surfaces as peripheral membraneproteins by embedding an amphipathichelix. Examples include members of the

perilipin family of proteins [e.g. perilipin,adipophilin, S3-12 and tail-interactingprotein of 47 kDa (TIP47)] (Brasaemle,2007). Whether a recently identifiedN-terminal hydrophobic sequence sharedbetween several LD proteins [e.g. theputative methyltransferases AAM-B(methyltransferase-like protein 7A) andALDI (associated with lipid droplet protein1)] uses a similar targeting mechanismremains to be determined (Zehmer et al.,2008). Surprisingly, a variety of proteinshave been detected in the hydrophobic coreof LDs (Robenek et al., 2005), includingthe perilipin family of proteins. How suchproteins are transported in and out of LDs,however, and whether they are nativelyfolded in the LD are not clear.

Lipid-droplet formationThe life cycle of LDs begins when fattyacids that are carried extracellularly byalbumin and lipoproteins enter cells. Fattyacids are released from triacylglycerols inlipoproteins by lipoprotein lipase, andenter cells by passive diffusion facilitatedby fatty-acid transport proteins or fatty-acid translocase (Ehehalt et al., 2006;Schaffer and Lodish, 1994). Fatty acids canalso be synthesized de novo fromcarbohydrates in many cell types.

Next, fatty acids enter a bioactive poolthrough conjugation to CoA, forming fattyacyl-CoA, in an energy-requiring reaction.Fatty acyl-CoA is used by glycerolipid-synthesis enzymes (glycerol-3-phosphateacyltransferase and sn-1-acylglycerol-3-phosphate acyltransferase) in the ER toultimately generate diacylglycerols.Diacylglycerols are either convertedto neutral lipids (triacylglycerols) byDGAT enzymes or enter phospholipid-synthesis pathways. How the flux betweenthese pathways is regulated is unknown.

In contrast to fatty acids, sterols areprimarily taken up into cells throughendocytosis and lysosomal degradation oflipoproteins. Most cells can also synthesizesterols. Excess sterols are converted tosterol esters through conjugation with fattyacyl-CoA in a reaction that is catalyzedby sterol-O-acyltransferases (e.g. acyl-CoA:cholesterol acyltransferase) in the ER.

Thus, neutral lipids that are found in LDcores are synthesized in the ER. How theselipids accumulate and form LDs is mostlyunknown. The canonical model posits thatneutral lipids form a lens of oil in the ER

bilayer that subsequently ‘buds’ from themembrane (the ER-budding model), takingwith it phospholipids from the cytosolicleaflet. Although the model has substantialsupport, this process has not been observeddirectly. In a variant of this model, the ER-domain model, LDs remain connected tothe ER and are lipid-containing protrusionsof the ER membrane, forming a specializedER domain.

Alternative models for LD formation havebeen proposed. In the bicelle model(Ploegh, 2007), neutral lipids accumulatebetween the leaflets of the ER membranebut, instead of budding, nascent LDs areexcised from the membrane, taking withthem phospholipids from both thecytosolic and luminal leaflets. This modelwas suggested to explain how largeunfolded proteins or viruses might escapefrom the ER lumen into the cytosol. In thevesicular-budding model (Walther andFarese, 2008), small bilayer vesicles thatremain tethered to the ER membraneare used as a platform for making LDs.Newly synthesized neutral lipids arepumped into the vesicle bilayer and fillthe intermembrane space, eventuallysqueezing the vesicular lumen so that itbecomes a small inclusion inside the LDs.Clues that help to decipher how LDs areformed might be provided by studyingseipin, an ER protein that is integral to LDformation (Fei et al., 2008; Szymanskiet al., 2007).

In lipoprotein-producing cells, such asintestinal enterocytes or hepatocytes,neutral lipids can also be directed from theER bilayer into the ER lumen to associatewith apolipoprotein B for secretion(Fujimoto et al., 2008). How the amount ofneutral lipids entering the storage versusthe secretion pathway is determined ismostly unknown.

Lipid-droplet growthThe size of LDs varies tremendously, withdiameters ranging from as small as20-40 nm (Stobart et al., 1986) to 100 µm(in white adipocytes), and, clearly, LDs cangrow in size. How do LDs grow sodramatically?

One possibility is that LDs, like balloons,expand as single organelles. If LDs remainattached to the ER, proteins and newlysynthesized lipids could diffuse laterally tothe LDs. If LDs are detached from the ER,these proteins and lipids must be

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transported to the LDs, perhaps viavesicular transport. This would pose aproblem of topology, as a vesicular bilayermembrane would have to fuse with amonolayer surface at the LD.Alternatively, neutral lipids in the corecould be produced locally by enzymes,such as DGATs, that are targeted to the LDsurface. In either scenario, the increase involume of neutral lipids would need tobe matched by a corresponding increaseof phospholipids at the surface. Inagreement with this notion, a keyenzyme of phospholipid synthesis,CTP:phosphocholine cytidylyltransferase(CCT), is localized to LD surfaces duringtheir growth (Guo et al., 2008).

Fusion of smaller LDs to form larger LDsis also likely to contribute to LD growth(e.g. Guo et al., 2008), and models thatimplicate SNARE proteins and motorproteins in LD fusion have been proposed(Boström et al., 2007; Olofsson et al.,2008). A fusion mechanism wouldalleviate the requirement for phospholipidsynthesis during the growth of LDs,because the surface:volume ratio decreaseswith fusion.

Lipid-droplet mobilizationNeutral lipids in LDs are mobilized bylipases to provide metabolic energy(through the oxidation of fatty acids) andlipids for membrane synthesis (Brasaemle,2007; Ducharme and Bickel, 2008;Zechner et al., 2005). In adipocytes, thislipolysis is triggered by hormonal,nutritional or inflammatory (such as tumornecrosis factor-α) signals. For example,catecholamines bind to β-adrenergicG-protein-coupled receptors at the plasmamembrane and activate adenylyl cyclase,generating cAMP. This second messengeractivates protein kinase A, which directlyphosphorylates perilipin and hormone-sensitive lipase (HSL). Hormone-stimulated phosphorylation of perilipinreleases CGI-58 from the CGI-58–perilipincomplex, freeing CGI-58 to activate ATGL(Yamaguchi et al., 2007), and recruitsphosphorylated HSL to the LD surfaces.Together, ATGL and HSL hydrolyzetriacylglycerols to fatty acids andmonoacylglycerols, which are furthercatabolized to yield glycerol and fattyacids. The partially hydrolyzedintermediates (diacylglycerols andmonoacylglycerols) can also be used tosynthesize phospholipids. Mutations inCGI-58 impair lipolysis (Igal and

Coleman, 1998; Lass et al., 2006),implicating it as a key cofactor. CGI-58also has lysophosphatidic-acid-specificacyltransferase activity (Ghosh et al.,2008) of unclear significance. The fattyacids that are liberated from lipolysis maybe activated to acyl-CoA and transported tomitochondria for β-oxidation to providecellular ATP, may enter the nucleus, wherethey act as ligands for nuclear hormonereceptors and regulate gene transcription,or may be released from the cells toprovide fuel or signaling molecules forother cells or tissues.

During lipolysis, LDs might undergofission, which would dramatically increasethe surface area of LDs and enable lipasesto better access the neutral-lipid cores.Fission of LDs has been observed inadipocytes after massive lipolyticstimulation (Marcinkiewicz et al., 2006).As the surface area of LDs expands withfission, more surface phospholipids wouldbe required. This requirement mightexplain why a reduction in phospholipidsynthesis through the knockdown of CCTleads to a defect in lipolysis (Guo et al.,2008).

Lipid droplets interact with othercellular organellesThere is increasing evidence that LDsdynamically interact with other cellularorganelles. In particular, LDs are oftenfound in close approximation with the ER,mitochondria, endosomes, peroxisomesand the plasma membrane (Goodman,2008; Murphy et al., 2008). The functionsof these interactions are still largelyunknown. These organelle associationsmight facilitate the exchange of lipids,either for anabolic growth of LDs or fortheir catabolic breakdown. Alternatively,LDs might provide a means of transportinglipids between organelles within the cell,much like lipoproteins transport lipidsbetween tissues via the blood. Some of theinteractions between LDs and otherorganelles might be mediated andregulated by Rab GTPases, which havebeen found on LDs (Liu et al., 2008).

Unexpected functions for lipiddropletsBesides storing key lipids, recent studiessuggest that LDs might have other functionsin cellular physiology or pathology. Forexample, LDs might act as the protectivereservoir for unfolded proteins or othercompounds (that are sequestered in the

organic phase) to prevent harmfulinteractions with other cellular components(Ohsaki et al., 2006; Welte, 2007).

The intracellular pathogen C. trachomatisinduces the accumulation of LDs aroundthe bacteria-replication vacuole andappears to use LD components forreplication (Cacchiaro et al., 2008; Kumaret al., 2006). Similarly, the hepatitis Cvirus appears to use LDs as the platformfor viral assembly, and blocking theassociation of the hepatitis C core proteinwith LDs impairs viral replication(Miyanari et al., 2007). A betterunderstanding of these LD-pathogeninteractions might provide new avenuesfor therapeutic interventions.

PerspectivesThe past several years have witnessed aboom in research on the cellular biology ofLDs. However, almost all mechanisticdetails concerning LDs are unclear. Howexactly are LDs formed? How are proteinstargeted to LDs? How is fusion and fissionof LDs regulated? Do LDs traffic betweenorganelles? During lipolysis, how dolipases access neutral lipids in the LDcore? Answers to these exciting questionswill reveal much about the basicmechanisms of cellular lipid and energymetabolism, and might provide usefulknowledge for therapeutic andbiotechnological applications.

We thank Peter Walter, Neil Sheehy, and members ofthe Farese and Walther laboratories for helpfuldiscussion and comments on the manuscript; DarylJones for manuscript preparation; and Gary Howardand Stephen Ordway for editorial assistance. Thiswork was supported by NIH grant R21-DK78254 (toR.V.F., Jr), a David and Mary Phillips postdoctoralfellowship award (to Y.G.), the International HumanFrontier Science Program Organization (T.C.W.), theJ. David Gladstone Institutes (Y.G, K.R.C. and R.V.F.,Jr), and the Max-Planck Society (T.C.W.). Depositedin PMC for release after 12 months.

ReferencesBartz, R., Li, W. H., Venables, B., Zehmer, J. K., Roth,M. R., Welti, R., Anderson, R. G., Liu, P. andChapman, K. D. (2007a). Lipidomics reveals thatadiposomes store ether lipids and mediate phospholipidtraffic. J. Lipid Res. 48, 837-847.Bartz, R., Zehmer, J. K., Zhu, M., Chen, Y., Serrero,G., Zhao, Y. and Liu, P. (2007b). Dynamic activity oflipid droplets: protein phosphorylation and GTP-mediatedprotein translocation. J. Proteome Res. 6, 3256-3265.Boström, P., Andersson, L., Rutberg, M., Perman, J.,Lidberg, U., Johansson, B., Fernandez-Rodriguez, J.,Ericson, J., Nilsson, T., Borén, J. et al. (2007). SNAREproteins mediate fusion between cytosolic lipid dropletsand are implicated in insulin sensitivity. Nat. Cell Biol. 9,1286-1293.Brasaemle, D. L. (2007). The perilipin family ofstructural lipid droplet proteins: stabilization of lipiddroplets and control of lipolysis. J. Lipid Res. 48, 2547-2559.

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Brown, D. A. (2001). Lipid droplets: proteins floating ona pool of fat. Curr. Biol. 11, R446-R449.Cacchiaro, J. L., Kumar, Y., Fischer, E. R., Hackstadt,T. and Valdivia, R. H. (2008). Cytoplasmic lipid dropletsare translocated into the lumen of the Chlamydiatrachomatis parasitophorous vacuole. Proc. Natl. Acad.Sci. USA 105, 9379-9384.Ducharme, N. and Bickel, P. (2008). Lipid droplets inlipogenesis and lipolysis. Endocrinology 149, 942-949.Ehehalt, R., Füllekrug, J., Pohl, J., Ring, A.,Herrmann, T. and Stremmel, W. (2006). Translocationof long chain fatty acids across the plasma membrane-lipidrafts and fatty acid transport proteins. Mol. Cell Biochem.284, 135-140.Fei, W., Shui, G., Gaeta, B., Du, X., Kuerschner, L., Li,P., Brown, A., Wenk, M., Parton, R. and Yang, H.(2008). Fld1p, a functional homologue of human seipin,regulates the size of lipid droplets in yeast. J. Cell Biol.180, 473-482.Fujimoto, T., Ohsaki, Y., Cheng, J., Suzuki, M. andShinohara, Y. (2008). Lipid droplets: a classic organellewith new outfits. Histochem. Cell Biol. 130, 263-279.Ghosh, A. K., Ramakrishnan, G., Chandramohan, C.and Rajasekharan, R. (2008). CGI-58, the causativegene for Chanarin-Dorfman syndrome, mediates acylationof lysophosphatidic acid. J. Biol. Chem. 283, 24525-24533.Goodman, J. M. (2008). The gregarious lipid droplet. J.Biol. Chem. 283, 28005-28009.Guo, Y., Walther, T. C., Rao, M., Stuurman, N.,Goshima, G., Terayama, K., Wong, J. S., Vale, R. D.,Walter, P. and Farese, R. V., Jr (2008). Functionalgenomic screen reveals genes involved in lipid-dropletformation and utilization. Nature 453, 657-661.Igal, R. A. and Coleman, R. A. (1998). Neutral lipidstorage disease: a genetic disorder with abnormalities inthe regulation of phospholipid metabolism. J. Lipid Res.39, 31-43.Kuerschner, L., Moessinger, C. and Thiele, C. (2008).Imaging of lipid biosynthesis: how a neutral lipid enterslipid droplets. Traffic 9, 338-352.Kumar, Y., Cocchiaro, J. and Valdivia, R. H. (2006).The obligate intracellular pathogen chlamydia trachomatistargets host lipid droplets. Curr. Biol. 16, 1646-1651.Lass, A., Zimmermann, R., Haemmerle, G., Riederer,M., Schoiswohl, G., Schweiger, M., Kienesberger, P.,

Strauss, J. G., Gorkiewicz, G. and Zechner, R. (2006).Adipose triglyceride lipase-mediated lipolysis ofcellular fat stores is activated by CGI-58 and defectivein Chanarin-Dorfman Syndrome. Cell Metab. 3, 309-319.Liu, P., Bartz, R., Zehmer, J., Ying, Y. and Anderson,R. (2008). Rab-regulated membrane traffic betweenadiposomes and multiple endomembrane systems.Methods Enzymol. 439, 327-337.Marcinkiewicz, A., Gauthier, D., Garcia, A. andBrasaemle, D. (2006). The phosphorylation of serine 492of perilipin a directs lipid droplet fragmentation anddispersion. J. Biol. Chem. 281, 11901-11909.Martin, S. and Parton, R. G. (2006). Lipid droplets: aunified view of a dynamic organelle. Nat. Rev. Mol. Cell.Biol. 7, 373-378.Miyanari, Y., Atsuzawa, K., Usuda, N., Watashi, K.,Hishiki, T., Zayas, M., Bartenschlager, R., Wakita, T.,Hijikata, M. and Shimotohno, K. (2007). The lipiddroplet is an important organelle for hepatitis C virusproduction. Nat. Cell Biol. 9, 1089-1097.Murphy, S., Martin, S. and Parton, R. G. (2008). Lipiddroplet-organelle interactions; sharing the fats. Biochim.Biophys. Acta [Epub ahead of print] doi:10.1016/j.bbalip.2008.07.004.Ohsaki, Y., Cheng, J., Fujita, A., Tokumoto, T. andFujimoto, T. (2006). Cytoplasmic lipid droplets are sitesof convergence of proteasomal and autophagicdegradation of apolipoprotein B. Mol. Biol. Cell 17, 2674-2683.Olofsson, S. O., Boström, P., Andersson, L., Rutberg,M., Levin, M., Perman, J. and Borén, J. (2008).Triglyceride containing lipid droplets and lipid droplet-associated proteins. Curr. Opin. Lipidol. 19, 441-447.Ploegh, H. (2007). A lipid-based model for the creation ofan escape hatch from the endoplasmic reticulum. Nature448, 435-438.Robenek, H., Robenek, M. and Troyer, D. (2005). PATfamily proteins pervade lipid droplet cores. J. Lipid Res.46, 1331-1338.Schaffer, J. E. and Lodish, H. F. (1994). Expressioncloning and characterization of a novel adipocyte longchain fatty acid transport protein. Cell 79, 427-436.Stobart, A. K., Stymne, S. and Höglund, S. (1986).Safflower microsomes catalyse oil accumulation in vitro:a model system. Planta 169, 33-37.

Stone, S. J., Levin, M. C. and Farese, R. V., Jr (2006).Membrane topology and identification of key functionalamino acid residues of murine acyl-CoA:diacylglycerolacyltransferase-2. J. Biol. Chem. 281, 40273-40282.Stone, S. S., Levin, M. C., Zhou, P., Han, J., Walther,T. C. and Farese, R. V., Jr (2009). The endoplasmicreticulum enzyme, DGAT2, is found in mitochondria-associated membranes and has a mitochondrial targetingsignal that promotes its association with mitochondria. J.Biol. Chem. 284, 5352-5361.Szymanski, K., Binns, D., Bartz, R., Grishin, N., Li, W.,Agarwal, A., Garg, A., Anderson, R. and Goodman, J.(2007). The lipodystrophy protein seipin is found atendoplasmic reticulum lipid droplet junctions and isimportant for droplet morphology. Proc. Natl. Acad. Sci.USA 104, 20890-20895.Walther, T. C. and Farese, R. V., Jr (2008). The life oflipid droplets. Biochim. Biophys. Acta [Epub ahead ofprint] doi:10.1016/j.bbalip.2008.10.009.Welte, M. A. (2007). Proteins under new management:lipid droplets deliver. Trends Cell Biol. 17, 363-369.Yamaguchi, T., Omatsu, N., Morimoto, E., Nakashima,H., Ueno, K., Tanaka, T., Satouchi, K., Hirose, F. andOsumi, T. (2007). CGI-58 facilitates lipolysis on lipiddroplets but is not involved in the vesiculation of lipiddroplets caused by hormonal stimulation. J. Lipid Res. 48,1078-1089.Zechner, R., Strauss, J. G., Haemmerle, G., Lass, A.and Zimmermann, R. (2005). Lipolysis: pathway underconstruction. Curr. Opin. Lipidol. 16, 333-340.Zehmer, J. K., Bartz, R., Liu, P. and Anderson, R. G.(2008). Identification of a novel N-terminal hydrophobicsequence that targets proteins to lipid droplets. J. Cell Sci.121, 1852-1860.

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Cell Science at a Glance on the WebElectronic copies of the poster insert areavailable in the online version of this articleat jcs.biologists.org. The JPEG images canbe downloaded for printing or used asslides.

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