Lipid droplets (LDs) are found in most organisms where they serve to store energy in form of neutral lipids. They are formed at the endoplasmic reticulum (ER) membrane where the neutral lipid synthesizing enzymes are located. Recent results indicate that LDs 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 LDs, however, is still ill-defined. Here we probe the topology of LD biogenesis by artificially targeting proteins that have high affinity for LDs inside the luminal compartment of the ER. Unexpectedly, these proteins still localize to LDs in both yeast and mammalian cells, indicating that LDs are accessible from within the ER lumen. These data are consistent with a model in which LDs form a specialized domain in the ER membrane that is accessible from both the cytosolic and the ER luminal side.
- Received March 11, 2016.
- Accepted August 17, 2016.
- © 2016. Published by The Company of Biologists Ltd