Biogenesis and metabolism of LDs. (A and B) The biogenesis of LDs. (A) Schematic representation of the processes occurring in the ER membranes during LD biogenesis. After esterification, a neutral lipid lens separates in the ER bilayer. The lens laterally moves into nascent LDs, which progressively grow into mature LDs. Neutral lipid synthesis also occurs locally on LDs. LD proteins access the LD monolayer laterally from the ER membranes (red) or from the cytosol (blue) to regulate LD function. Accessory proteins, such as seipin, cooperate during the process. (B) The image illustrates LD formation (red) on ER membranes (green) in COS-7 cells that were treated for 7.5 min with oleic acid to induce LD formation. A specific marker for nascent LDs, a peptide formed by Aldi’s hydrophobic domain and caveolin-1 LD-targeting motif, was used to visualize LDs. Adapted with permission from the Journal of Cell Biology. (C) Main metabolic pathways involved in LDs biogenesis and metabolism. Fatty acids obtained from the extracellular environment or formed de novo by lipogenesis are esterified into triacylglycerols and stored within LDs in cells. Cholesterol is esterified into cholesteryl esters and accumulated within LDs. When these nutrients are needed, lipolysis is activated by the actions of LD lipases that produce fatty acids to be oxidized in mitochondria to generate ATP or produce molecules such as phospholipids or inflammatory mediators. Enzymes (detailed in boxes) are written with blue letters and intermediate molecules with gray letters. Blue arrows indicate fluxes during LD biogenesis and red arrows reactions occurring during LD catabolism.