Mechanisms of Lipid Droplet Protein Targeting

Project Summary LDs are essential organelles for lipid storage and metabolism. They are defined by a set of specific proteins on their surface, many of which accumulate and are implicated in etiology of common human pathologies, such as hepatic steatosis and cardiovascular disease. Recent advancements in understanding lipid droplet (LD) biology, mostly derived from studying Drosophila cells, have illuminated key aspects of protein targeting to LDs. However, key challenges remain in determining how these pathways function in human cells, how physiologically important LD proteins (e.g., GPAT4 or ATGL) target LDs and what the structural basis of LD protein targeting is. We have developed innovative methods to investigate LD targeting mechanisms, including single-molecule analysis and new assays for studying protein dynamics on LDs. We also will address the open question how proteins are removed from LDs under conditions of LD turnover. Findings from this work will address fundamental and yet unclear questions in cell biology. Since LD proteins are targets for therapeutic intervention for prevalent diseases, this work may also pave the way for devising novel therapeutic strategies against diseases linked to lipid dysregulation.