Fat storage is an essential mechanism whereby cells store energy that can be later used to perform basal functions when food intake is reduced or insufficient. In cells, fat is deposited in organelles called lipid droplets (LDs). LDs are not mere inert storage pools, but they are active sites of lipid metabolism and remodeling. Furthermore, they are involved in numerous diseases, such as obesity, diabetes, cancer, and viral infection (Welte and Gould, 2017). Despite this central role in important physiological and pathological processes, the general biology of LDs is poorly understood. This is due to the unique structure of LDs, featuring a core of neutral lipids (NLs), surrounded by a monolayer of phospholipids (PLs). As a consequence of this peculiar composition and organization, the mechanism of LD formation remains largely unclear. The general consensus is that NLs are produced and stored between the two leaflets of the endoplasmic reticulum (ER) bilayer (Figure 1A); as the concentration of NLs exceeds a certain threshold, they aggregate in lenses (Figure 1B), that grow into nascent LDs (Figure 1C). Subsequently LDs bud from the ER bilayer toward the cytosol (Figure 1D) and, depending on the organism, they can either stay connected to the ER (Figure 1E) or detach in the cytosol (Figures 1E,F) (Wilfling et al., 2014b).
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Zoni et al. (2019) studied this question.