The life of lipid droplets

Abstract

Lipid droplets are the least characterized of cellular organelles. Long considered simple lipid storage depots, these dynamic and remarkable organelles have recently been implicated in many biological processes, and we are only now beginning to gain insights into their fascinating lives in cells. Here we examine what we know of the life of lipid droplets. We review emerging data concerning their cellular biology and present our thoughts on some of the most salient questions for investigation.

Fig. 1

Examples of lipid droplets in eukaryotic cells. Lipid droplets stained with BODIPY (green) in (a) S. cerevisiae, (b) Drosophila S2 cells [nuclei are stained blue with 4′,6-diamidino-2-phenylindole (DAPI)], and (c) murine adipocytes derived from embryonic fibroblasts (image courtesy of R. Streeper). (d) Lipid droplets (bright round organelles) in a single adipocyte derived from OP9 cells (phase contrast, image courtesy of C. Harris). (e) Lipid droplets stained with osmium tetroxide in intestinal enterocytes (arrow indicates an enterocyte that is filled with numerous dark-stained lipid droplets). (f) Electron micrograph of macrophage foam cells in a murine atherosclerotic lesion. Lipid droplets appear as round, empty objects. (g) Section of murine white adipose tissue showing large unilocular lipid droplets (empty spaces) that occupy most of the cytoplasm in white adipocytes. (h) High magnification electron micrograph of a single lipid droplet (large amorphous sphere) in a rat hepatoma cell (image courtesy of S. Stone and J. Wong).

Fig. 2

Models of lipid-droplet biogenesis. (Left) Model 1: Lipid droplet biogenesis by ER budding. Neutral lipids (orange) are synthesized by neutral lipid-synthesizing enzymes (NLSE) and bulge from the outer leaflet of the ER membrane (red). The nascent droplet may be coated by proteins (dark blue) that facilitate the budding process. (Middle) Model 2: Bilayer excision. Newly synthesized neutral lipids accumulate between the inner (blue) and outer (red) leaflets of the ER membrane and cause bulging. This entire lipid lens is then excised from the ER, leaving a transient hole in the membrane. ER contents (yellow) might leak through this hole into the cytosol. (Right) Model 3: Vesicular budding. A vesicle containing both leaflets of the ER membrane (red and blue) and a lumen (yellow) is formed by the vesicular budding machinery (green) at the ER membrane. The vesicle is subsequently tethered to the ER, where NLSEs (grey) fill the intramembranous space with neutral lipids (orange). The luminal space (yellow) is compressed, and its contents may leak into the cytosol. This process may trap luminal proteins within a compartment of the lipid droplet.

Fig. 3

Dynamic processes linked to lipid-droplet biology. Different events in the dynamic life of a lipid droplet (orange interior representing the neutral lipids and a red line indicating the bounding monolayer of phospholipids) are shown in the four panels. In the “fusion” panel, blue and purple protein complexes represent SNARE proteins and tethering complexes, respectively. In the “fragmentation” panel, green proteins covering the lipid droplet during fragmentation indicate COPI/Arf1 coat proteins. During lipid droplet transport, motor proteins (blue) mediate the movement of droplets along microtubules (red).