RT Journal Article
SR Electronic
T1 Lipid droplet biogenesis is a liquid phase separation spatially regulated by seipin and membrane curvature
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 777466
DO 10.1101/777466
A1 Valeria Zoni
A1 Pablo Campomanes
A1 Rasha Khaddaj
A1 Abdou Rachid Thiam
A1 Roger Schneiter
A1 Stefano Vanni
YR 2019
UL http://biorxiv.org/content/early/2019/09/20/777466.abstract
AB Cells store energy in the form of neutral lipids packaged into micrometer-sized organelles named lipid droplets (LDs). These structures emerge from the endoplasmic reticulum (ER), but their biogenesis remains poorly understood. Using molecular simulations, we found that LD formation proceeds via a liquid-liquid phase separation process that is modulated by the physical properties and lipid composition of the ER membrane. LD formation is promoted at ER sites characterized by high membrane curvature and by the presence of the ER-associated protein seipin, that cause accumulation of triglycerides by slowing down their diffusion in the membrane. Our data indicate how a combination of membrane physical properties and protein scaffolding is used by the cell to regulate a broad and energetically-efficient biophysical process such as liquid/liquid phase separation to achieve LD biogenesis.