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.

FIGURE 1.

LDs are surrounded by ER, mitochondria, and peroxisomes, which contribute to synthesis of lipids to be assembled into LDs. The insets depict areas where LDs come into close contact with the ER and mitochondria (left) and peroxisomes as well as the ER (right). TAGs are synthesized by enzymes associated with LDs (dark red), the ER (green), and mitochondria (brown). ACSs localize to the ER, LDs, and mitochondria and activate fatty acids for esterification or catabolism. Several isoforms of GPAT localize to the ER and mitochondria and initiate the reactions to build complex lipids. Proteins in the AGPAT family add a second acyl chain (red) to 1-acylglycerol 3-phosphate at the ER. PAP removes the phosphate group so that DGAT can add the final acyl chain to complete the synthesis of TAG. DGAT2 is found on the ER and in close proximity to LDs. TAG is then packaged into the core of LDs. Peroxisomes (cyan) are the sole location for ether lipid synthesis, which requires the enzymes dihydroxyacetone-phosphate acyltransferase (DHAPAT) and alkyldihydroxyacetone-phosphate synthase (ADHAPS). LDs have both ether-linked neutral lipids and ether-linked phospholipids. Members of the perilipin family localize primarily to LDs; perilipins 3 and 4 also localize to the ER, particularly at regions where neutral lipids accumulate. FIT1 and FIT2 localize to the ER and contribute to LD formation and maturation. FSP27 (also called CIDEC) localizes to LDs, where it affects LD size and catabolism of stored TAG. Seipin localizes to contact points between LDs and the ER.

FIGURE 2.

Earliest deposits of neutral lipid are found along ER. OP9 preadipocytes ectopically expressing HA epitope-tagged AGPAT2 were incubated with fatty acids to induce LD biogenesis. Cells were fixed and stained with anti-HA antibody to reveal the ER (green) and with anti-perilipin 3 antibody to detect LDs (red). Scale bar = 2 μm.