Lipid droplets are dynamic membrane aggregates that store and release lipids for cellular energy and biosynthesis. They also mediate cell signaling, organelle and mitochondrial dynamics, as well as gene transcription. In mammals, a large number of proteins are associated with lipid droplets (the lipid droplet proteome). These proteins are involved in processes that are directly or indirectly related to the lipid droplets and their metabolism. They include protein complexes involved in lipid metabolism and signaling, redox metabolism, autophagy, ubiquitination, membrane trafficking, gene transcription and the immune system.
A key function of lipid droplets is their ability to buffer excess fats and prevent lipotoxicity. This is achieved by sequestering fatty acids in the core of the lipid droplets as triacylglycerol and mobilizing them for metabolic processes or for membrane biosynthesis. Abnormalities in fat storage in lipid droplets lead to conditions such as obesity, fatty liver and insulin resistance.
The composition of lipid droplets and the mechanisms that control their formation, growth, fusion and detachment are major areas of research. Recent advances have been made in understanding the machinery that regulates lipid droplet biogenesis and many of the proteins associated with them. Other recent discoveries have revealed the existence of contacts between lipid droplets and mitochondria, endoplasmic reticulum, lysosomes, Golgi apparatus, and peroxisomes. These are mediated by protein tethers and membrane bridges that enable bidirectional transfer of lipids and proteins.
In addition, lipid droplets display unique properties when compared to other membranes. For example, lipid drops have a propensity to display packing defects that appear to be optimal for binding amphipathic amino acid-containing proteins such as CCTa and PLIN4. These proteins are known to bind to the hydrophobic regions of phospholipids in the interior of lipid droplets.
Lipid droplets also exhibit a dynamic morphology, which allows them to form spherical structures or extend processes that are referred to as pexopodia. The extension of pexopodia is thought to allow luminal peroxisome enzymes to access lipid droplet-stored triacylglycerol, to facilitate the transfer of proteins to and from lipid droplets, and to provide a physical link between lipid droplets and other organelles.
The development of a full understanding of the dynamics and role of lipid droplets will require combining experimental and computational approaches to identify the complex set of processes that interact with them. These will include studies of lipid droplet assembly, turnover and morphology; the mechanisms by which they are tethered to ER membranes; and their interactions with other organelles. Moreover, the identification of lipid droplet-associated proteins will be crucial to understand how the lipid droplets are regulated in different cells. This will allow the development of strategies to target these proteins for therapeutic interventions.