Getting a handle on lipid droplets: Insights into ER-lipid droplet tethering

Abstract

Lipid droplets (LDs) are hubs for lipid metabolism that form membrane contact sites with multiple organelles. In this issue, Hariri et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808119) reveal the functions of Mdm1-mediated endoplasmic reticulum (ER)-LD tethering in yeast and Datta et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808133) identify a role for the Mdm1 orthologue, Snx14, as an ER-LD tether that regulates lipid metabolism in human cells.

Figure 1.

Model of Mdm1 and Snx14 in the formation and regulation of LD MCSs. (A) Yeast Mdm1 domain structure. (B) Mdm1 functions as a tri-organelle tether, physically linking the ER, vacuole, and LDs. Mdm1 binds FFA and recruits Faa1, providing high local concentrations of activated FA that promote efficient neutral lipid synthesis and prevent lipotoxicity. (C) Human Snx14 domain structure. (D) Snx14 acts as an ER–LD tether and promotes LD biogenesis. AH, amphipathic helix.