Packaging of Fat: An Evolving Model of Lipid Droplet Assembly and Expansion

Abstract

Lipid droplets (LDs) are organelles found in most types of cells in the tissues of vertebrates, invertebrates, and plants, as well as in bacteria and yeast. They differ from other organelles in binding a unique complement of proteins and lacking an aqueous core but share aspects of protein trafficking with secretory membrane compartments. In this minireview, we focus on recent evidence supporting an endoplasmic reticulum origin for LD formation and discuss recent findings regarding LD maturation and fusion.Eukaryotic cells produce and traffic membranes that maintain intracellular compartments that facilitate regulation of metabolism by controlling the subcellular localization of metabolites, the concentrations of enzymes and substrates to optimize enzyme reactions, and the isolation of toxic metabolites. Fatty acids supply a major source of energy for organisms but also can be toxic. Cells escape cytotoxicity by esterifying fatty acids into neutral lipids and packaging them into lipid droplets (LDs) 3 coated with phospholipids and proteins. When cells are exposed to excess fatty acids, protein-coated LDs replete with neutral lipids bud from membranes of the endoplasmic reticulum (ER). When levels of exogenous fatty acids wane, the surface proteins of nascent LDs are exchanged for other proteins that serve various functions on mature LDs. Recent studies have established LDs as a distinct organelle.The protein components of LDs have been increasingly studied over the past decade. In chordates and flies, members of the perilipin family of proteins are among the most abundant proteins coating LDs (1, 2). Perilipins interact with both lipid and cytosolic proteins, forming an amphipathic interface between stored lipids and the cytosol. LDs in the cells of various vertebrate tissues are coated with two to four types of perilipin; each unique combination of perilipins imparts tissue-specific management of lipid metabolism. The expression of perilipin 1 is limited to adipocytes of white and brown adipose tissue and steroidogenic cells of the adrenal cortex, testes, and ovaries; moreover, subcellular localization of perilipin 1 is essentially restricted to LDs. Perilipin 2 (formerly adipophilin/ADRP (adipose differentiation-related protein)) and perilipin 3 (formerly TIP47 (tail-interacting protein of 47 kDa)) are ubiquitously expressed and hence contribute to the protein coat of LDs in the majority of cells. Perilipin 2 localizes primarily to LDs. Perilipin 3 is stable in the cytoplasm of cells but rapidly associates with nascent LDs when cells are incubated with fatty acids to promote triacylglycerol (TAG) synthesis and storage. Perilipin 4 (formerly S3-12) is expressed primarily in adipocytes of white adipose tissue and localizes to buds of nascent LDs along the ER. Perilipin 5 (formerly MLDP (myocardial lipid droplet protein)/OXPAT (oxidative protein of the PAT family)/LSDP5 (lipid storage droplet protein 5)) is expressed in oxidative tissues, including cardiac and skeletal muscle, and in brown adipocytes. In addition...

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