Mechanisms and functions of lipid recycling for cellular metabolism

Harvard University, Cambridge MA

Investigators

Abstract

Project Summary/Abstract My lab seeks to address mechanisms of cellular fatty acid metabolism and their implication in cellular functions. Subcellular organelles called lipid droplets (LDs) play an integral role in lipid metabolism by storing lipids and buffering cellular fatty acid fluctuation to prevent lipotoxicity and to adequately provide lipid sources as needed. Much effort has focused on defining and elucidating the pathways governing LD formation, but less is known about how fatty acids are released from LDs in (patho)physiological circumstances. A major long-term goal of our research program is to understand how cells regulate fatty acid recycling pathways to control metabolism and signaling in health and disease. In the next five years, we will focus on two areas outlined in this proposal: 1) What are the regulatory mechanisms underlying the autophagic lipid degradation pathway? Lipophagy is a critical cellular pathway that degrades LDs to supply lipids for cellular functions. We recently discovered a specific lipophagy receptor, a crucial first step toward revealing the mechanisms of this pathway and its contribution to cellular lipid metabolism. Building on this foundational discovery, my lab will investigate the cell states and metabolic conditions in which the lipophagy pathway participates and its mechanistic foundations. 2) How are lipids trafficked within cells and utilized at inter-organelle membrane contact sites? Lipids recycled from LDs are essential for various cellular functions, including membrane biogenesis, energy production, and signal transduction. However, the process of how fatty acids traffic and find their destinations in cells remains elusive. My lab will elucidate how LDs crosstalk with various subcellular organelles to efficiently transfer lipids and support cellular metabolism. Our proposed research will reveal fundamental principles of lipid recycling mechanisms and contribute to the development of potential therapeutic strategies focused on defective lipid metabolism in various metabolic and neurodegenerative disorders.