Peng Li, Professor, School of Life Sciences, Tsinghua University

Lipid droplets (LDs) are dynamic sub-cellular organelles that store neutral lipids and play vital roles in metabolic homeostasis. Dysfunctional LD biogenesis or growth leads to disorders including obesity, fatty liver disease, diabetes, and atherosclerosis. We identified CIDE family proteins including CIDEA, CIDEB, and CIDEC as crucial factors in controlling LD growth through an LD fusion process. During this process, CIDE proteins are enriched at LD-LD contact sites through gel-like phase separation, which generates highly plastic fusion plates with unique lipid passageways for lipid transfer, leading to LD fusion. Importantly, we are able to reconstitute CIDEC-mediated LD fusion in vitro and identified PI4P as a specific factor to recruit CIDEC to LD surface. In addition, CLSTN3β, by localizing to ER-LD contact sites, inhibits CIDE proteins-mediated LD fusion, contributing to multilocular LD formation and promoting lipid utilization in brown adipocytes. Besides CIDE proteins, we will discuss various other regulatory factors in controlling LD dynamics and its interaction with other sub-cellular organelles. An-imaging based method in measuring lipolysis rate at a single LD level will also be described.