Lipid Droplets: Structure, Composition, Formation and Function. Connection with the Endoplasmic Reticulum

Abstract

Fatty acids (FAs) are important compounds either used for energy production through β-oxidation, for membrane lipid synthesis, or for production of lipid mediators (oxylipins) through oxidations. FAs are also cytotoxic and their cellular concentration has to be maintained low. To counteract their toxicity, cells esterify FAs into neutral lipids [triacylglycerols (TAGs) and steryl esters (SEs)], and enclose them into organelles named lipid droplets (LDs). Lipid droplets have a central core of neutral lipids (triglycerides, steryl esters, retinyl esters) surrounded by a single layer of amphipathic lipids (mostly phospholipids) and proteins. Lipid droplets (LDs) form between the leaflets of the endoplasmic reticulum (ER) membrane and consist of a neutral lipid core enclosed in a phospholipid monolayer with proteins. Mass spectrometric analyses of isolated LDs revealed some exclusive attributes of the phospholipids. In mammalian LDs, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are major species as in other membranes, but LDs also contain lysophosphatidylcholine and lysophosphatidylethanolamine with unsaturated fatty acids and the ether-linked form of PC and PE. Perilipins (i.e., perilipin1–5) are the first proteins that were identified in LDs. Perilipin1 in adipocytes and perilipin5 in oxidative cells (e.g., striated muscles) function both as a lipolytic barrier and a regulator of TG hydrolyzing enzymes. Ubiquitously expressed perilipin2 and perilipin3 also seem to act protectively against lipolysis. Cytosolic lipid droplets are active lipid-storage organelles that play a central role as reservoirs of metabolic energy and membrane precursors. These organelles are present in almost all cell types, from unicellular to pluricellular organisms. In spite of comparable structural organization, lipid droplets are heterogeneous in morphology, distribution and composition. The protein range related to lipid droplet controls the organelle dynamics. Different structural lipid droplet proteins are connected to specific lipolytic pathways. The role of these structural lipid droplet-connected proteins in the control of lipid droplet degradation and lipid store mobilization is very important. Additionally LDs, through the uptake of lipids, defend cells from lipotoxicity, liberate lipids as signaling molecules, and are implicated in protein degradation and endoplasmic reticulum (ER) stress responses.