Veijo Salo

The balance of intracellular neutral lipid (NL) flux in hepatocytes is critical for metabolic health: excessive lipid deposition in intracellular lipid droplets (LDs) leads to fatty liver disease, while excessive secretion of NLs within very-low-density lipoproteins (VLDLs) drives atherosclerosis. Despite these opposing outcomes, both LDs and VLDLs originate from the endoplasmic reticulum (ER) bilayer, yet the nanoscale coordination of their assembly remains poorly understood. This project seeks to resolve a fundamental question: how is NL fate determined in the ER?By integrating cutting-edge cell biology, cryo-correlative light and electron tomography (cryo-CLEM ET) with our newly developed localization tags, and lipid biophysics, I will construct a dynamic 4D model of LD and VLDL biogenesis within specialized ER subdomains. This research will uncover the intricate interplay between LD and VLDL assembly, elucidate the molecular mechanisms driving seipin conformational changes during LD formation, and reveal how lipid composition and biophysical properties define ER subdomains for NL partitioning.Through an interdisciplinary approach that bridges structural biology, live-cell imaging, and computational modeling, this project will provide an unprecedented molecular blueprint of hepatic NL flux. These insights will not only advance our fundamental understanding of lipid metabolism but also lay the groundwork for future therapeutic strategies targeting metabolic disorders.