Pre-existing bilayer stresses modulate triglyceride accumulation in the ER versus lipid droplets

• DOI: 10.7554/elife.62886
• Publication Date: 2021-02-01T13:01:42Z
• Authors: Valeria Zoni; Rasha Khaddaj; Pablo Campomanes; Abdou Rachid Thiam; Roger Schneiter; Stefano Vanni
• Keywords: Lipid droplet; Phosphatidylethanolamine; Organelle; Lipotoxicity

Cells store energy in the form of neutral lipids (NLs) packaged into micrometer-sized organelles named lipid droplets (LDs). These structures emerge from endoplasmic reticulum (ER) at sites marked by protein seipin, but mechanisms regulating their biogenesis remain poorly understood. Using a combination molecular simulations, yeast genetics, and fluorescence microscopy, we show that interactions between lipids’ acyl-chains modulate propensity NLs to be stored LDs, turn preventing or promoting accumulation ER membrane. Our data suggest diacylglycerol, which is enriched LD formation, promotes packaging together with ER-abundant lipids, such as phosphatidylethanolamine. On opposite end, short saturated antagonize fat storage LDs promote ER. results provide new conceptual understanding context homeostasis function.