Mature lipid droplets are accessible to ER luminal proteins

Abstract

Lipid droplets are found in most organisms where they serve to store energy in the form of neutral lipids. They are formed at the endoplasmic reticulum (ER) membrane where the neutral-lipidsynthesizing enzymes are located. Recent results indicate that lipid droplets remain functionally connected to the ER membrane in yeast and mammalian cells to allow the exchange of both lipids and integral membrane proteins between the two compartments. The precise nature of the interface between the ER membrane and lipid droplets, however, is still ill-defined. Here, we probe the topology of lipid droplet biogenesis by artificially targeting proteins that have high affinity for lipid droplets to inside the luminal compartment of the ER. Unexpectedly, these proteins still localize to lipid droplets in both yeast and mammalian cells, indicating that lipid droplets are accessible from within the ER lumen. These data are consistent with a model in which lipid droplets form a specialized domain in the ER membrane that is accessible from both the cytosolic and the ER luminal side.

The assembly of lipid droplets and their roles in challenged cells

“…The extrusion of neutral lipid from the ER into the bud does not typically result in total sequestration of neutral lipid away from the ER bilayer. If newly synthesized droplet proteins are diverted to the ER lumen instead of the cytosol, they still are able to target to droplets (Mishra et al , ). The simplest interpretation of this result is that the luminal ER surface apposed to the droplet is still bathed in neutral lipid that is continuous with the corresponding droplet and as such is recognized by droplet proteins.…”

Muscle Lipid Metabolism: Role of Lipid Droplets and Perilipins

“…LDs are limited by a phospholipid monolayer, which includes phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol [67]. This composition is similar to the endoplasmic reticulum (ER) membrane, supporting the idea that LDs are a specialized domain of the ER [68]. …”

Lipid droplet‐mediated lipid and protein homeostasis in budding yeast

“…Driven by additional neutral lipid synthesis, these lenses grow and nascent lipid droplets emerge from the ER toward the cytosol surrounded by a phospholipid monolayer connected to the ER by ER‐lipid droplet junctions. Subsequently, mature lipid droplets may remain connected or bud off and physically separate from the ER . ER‐associated biogenesis of lipid droplets seems evolutionarily conserved.…”