Lipid Droplets and the Management of Cellular Stress.

ABSTRACT

Lipid droplets are cytosolic fat storage organelles present in most eukaryotic cells. Long regarded merely as inert fat reservoirs, they are now emerging as major regulators of cellular metabolism. They act as hubs that coordinate the pathways of lipid uptake, distribution, storage, and use in the cell. Recent studies have revealed that they are also essential components of the cellular stress response. One of the hallmark characteristics of lipid droplets is their capacity to buffer excess lipids and to finely tune their subsequent release based on specific cellular requirements. This simple feature of lipid droplet biology, buffering and delayed release of lipids, forms the basis for their pleiotropic roles in the cellular stress response. In stressed cells, lipid droplets maintain energy and redox homeostasis and protect against lipotoxicity by sequestering toxic lipids into their neutral lipid core. Their mobility and dynamic interactions with mitochondria enable an efficient delivery of fatty acids for optimal energy production. Lipid droplets are also involved in the maintenance of membrane and organelle homeostasis by regulating membrane composition, preventing lipid peroxidation and removing damaged proteins and lipids. Finally, they also engage in a symbiotic relationship with autophagy and act as reservoirs of bioactive lipids that regulate inflammation and immunity. Thus, lipid droplets are central managers of lipid metabolism that function as safeguards against various types of cellular stress.