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-lipid-synthesizing 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 authors declare no competing or financial interests.
Conceptualization, S.M., R.K., S.C., V.S., C.J. and R.S.; Formal Analysis, R.K., S.C. and C.J.; Investigation, S.M., R.K., S.C., V.S. and C.J.; Writing, C.J. and R.S., Visualization, S.M., R.K., S.C., V.S. and C.J.; Supervision, C.J. and R.S.; Funding acquisition, C.J. and R.S.
This work was supported by the Canton of Fribourg; and by the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation).
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.189191.supplemental
- Received March 11, 2016.
- Accepted August 17, 2016.
- © 2016. Published by The Company of Biologists Ltd