Thematic minireview series on the lipid droplet, a dynamic organelle of biomedical and commercial importance.

The lipid droplet (also known as lipid particle and oil body) is a dynamic organelle whose boundary is surrounded by a phospholipidmonolayer andwhose inner core is composedmainly of triacylglycerol (TAG) and steryl esters. The monolayer surface is coated with an assortment of proteins that serve structural and metabolic functions. Although the existence of lipid droplets in mammalian cells, plants, yeast, and bacteria has been known for many years, a great deal of attention is currently being paid to the mechanismsof its formationandgrowthand themetabolismof its core components. Indeed, the lipid droplet is now appreciated because it plays important roles in lipid-based diseases and has commercial importancewith respect toproductionof cookingoils and biofuels. The first minireview by Dawn L. Brasaemle and Nathan E. Wolins, “Packaging of Fat: An EvolvingModel of Lipid Droplet Assembly and Expansion,” summarizes evidence supporting the following model of lipid droplet assembly. Nucleation initiates in the endoplasmic reticulum (ER) when diacylglycerol accumulates and attracts members of the perilipin family of structural lipid droplet proteins to patches of the ERwhere lipid droplets begin to emerge. Resident proteins of the ER, including seipin and fat storage-inducing transmembrane proteins FIT1 and FIT2, contribute to early assembly through as yet uncharacterizedmechanisms. After the nascent lipid droplet emerges, other organelles, including mitochondria and peroxisomes, contribute additional lipids. Changes in protein composition accompany droplet maturation. In most cells, lipid droplets are few and small, but in adipocytes (“professional” fat storing cells), the droplets enlarge to 100 m or larger. Adipocyte lipid droplets grow, in part, by fusion of smaller droplets; however, the mechanism of fusion is also poorly understood. Observations suggesting that the fat-specific protein FSP27 plays a role in lipid droplet expansion and perhaps fusion are discussed. Proteins associatedwith lipid droplets serve a vital role inmobilizing lipids at times of need; perilipins function to coordinate access of lipases to substrate lipids. Pathways of lipase delivery to lipid droplets share features with well characterized mechanisms of vesicular trafficking. Changes in the phospholipid monolayer surrounding the neutral lipid core accompany attrition of lipid droplets during lipolysis and also the expansion andmaturation of the droplets. Recent studies show that several steps in phospholipid biosynthesis occur in the immediate proximity of lipid droplets, either by recruitment of enzymes to lipid droplets or through increased association of ER membranes harboring enzymes with lipid droplets. Brasaemle and Wolins integrate current data on lipid droplet assembly into the frameworkof our understanding of basic cellular processes. The second minireview by Eva Herker and Melanie Ott, “Emerging Role of LipidDroplets inHost/Pathogen Interactions,” highlights recent findings on how viruses, bacteria, and parasites hijack lipid droplets to support their own replication. The tight physical and functional interaction of lipid droplets with pathogens has only recently become apparent. On one side, these interactions provide important new insights into the life cycles of the pathogens and might lead to new therapeutic interventions. On the other side, they increase our mechanistic understanding of lipid droplet biology by spotlighting unique aspects exploited by pathogens. Hepatitis C and dengue viruses need lipid droplets to produce infectious particles, and rotaviruses rely on them to form viroplasms, which contain the active viral RNA replication complexes.Bacteria suchasChlamydia trachomatisanddiversemycobacteria utilize lipid droplets as a source for energy substrates or phospholipids to support bacterial replication. Some pathogens haveevolvedstrategies toevade the immunesysteminvolving lipid droplets or to support their own survival by using these organelles as dumping grounds for toxic metabolites or proteins, as in the case of infections with Plasmodium falciparum or Reoviridae 1. There is considerable and increasing interest in the health consequences of diets rich in fat content. A large proportion of fat calories inWestern diets are derived from plant TAGs, or vegetable oils, which are mostly enriched in seed or oleaginous fruit tissues. AlthoughTAGs are assembled and packaged in plant tissues into lipid droplets by mechanisms that resemble those found in other eukaryotes, there are important differences in factors that regulate the supply of TAGs for lipid droplet biogenesis. In the third minireview by Kent D. Chapman and John B. Ohlrogge, “Compartmentation of Triacylglycerol Accumulation in Plants,” the multitude of pathways and recently discovered features of TAG accumulation in plants are reviewed, with an eye toward identifying gaps in knowledge thatwill be important to the general cell biology of storage lipidmetabolism.New ideas about fatty acid biosynthesis, acyl-CoA incorporation into phosphatidylcholine, andseveral acyl-CoA-independentpathways forTAGsynthesis all indicate that the accumulation of oils into lipid droplets in different plant tissues is farmore complex than thewell known stepwise acylation of glycerol by enzymes of theKennedy pathway.Genetic engineering approaches to alter the fatty acid composition of oilseeds fornutritional and industrial purposeshavemetwith limited success. It is certain that the future design of strategies to enhance the accumulation of TAGs in plant-derived tissues for food and biofuels will depend on improved appreciation for the metabolic complexity and flexibility of TAG formation and packaging. 1 To whom correspondence should be addressed. E-mail: [email protected]. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 4, p. 2272, January 20, 2012 © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.