Abstract 1535 Regulation of Coatomer II-mediated ER-to-Golgi trafficking of sphingolipids

Sphingomyelin plays a key role in cellular cholesterol homeostasis in part by binding to and sequestering cholesterol in organelle membranes. Using lipidomics and metabolic pulse-chase assays to monitor sphingolipid synthesis, we discovered that synthesis of very -long -chain (VLC) sphingomyelins is inversely regulated by cellular cholesterol levels; acute cholesterol depletion elicited a rapid induction of VLC--sphingolipid synthesis, increased trafficking of sphingolipids from the endoplasmic reticulum to the Golgi apparatus and plasma membrane, while cholesterol loading reduced VLC--sphingolipid synthesis.