Developmental Cell
Volume 50, Issue 1, 1 July 2019, Pages 25-42.e7
Journal home page for Developmental Cell

Article
Membrane Asymmetry Imposes Directionality on Lipid Droplet Emergence from the ER

https://doi.org/10.1016/j.devcel.2019.05.003Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Emergence of LDs from the ER into the cytosol is facilitated by phospholipid synthesis

  • Membrane imbalance in phospholipid density regulates the emergence side of model LDs

  • Model LDs emerge on the side with the higher monolayer surface coverage

  • Asymmetric membrane insertion of proteins regulates the emergence side of model LDs

Summary

During energy bursts, neutral lipids fabricated within the ER bilayer demix to form lipid droplets (LDs). LDs bud off mainly in the cytosol where they regulate metabolism and multiple biological processes. They indeed become accessible to most enzymes and can interact with other organelles. How such directional emergence is achieved remains elusive. Here, we found that this directionality is controlled by an asymmetry in monolayer surface coverage. Model LDs emerge on the membrane leaflet of higher coverage, which is improved by the insertion of proteins and phospholipids. In cells, continuous LD emergence on the cytosol would require a constant refill of phospholipids to the ER cytosolic leaflet. Consistent with this model, cells deficient in phospholipids present an increased number of LDs exposed to the ER lumen and compensate by remodeling ER shape. Our results reveal an active cooperation between phospholipids and proteins to extract LDs from ER.

Keywords

cytosolic lipid droplet
directional budding
membrane asymmetry
phospholipid biosynthesis
protein binding
asymmetric surface tensions

Cited by (0)

6

Lead Contact