The assembly of lipid droplets and their roles in challenged cells

Abstract

Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they do not work in isolation. They respond to stimuli initiated either on the cell surface or in the cytoplasm as conditions change. Cellular stresses such as starvation and invasion are internal insults that evoke changes in droplet metabolism and dynamics. This review will first outline lipid droplet assembly and then discuss how droplets respond to stress and in particular nutrient starvation. Finally, the role of droplets in viral and microbial invasion will be presented, where an unresolved issue is whether changes in droplet abundance promote the invader, defend the host, to try to do both. The challenges of stress and infection are often accompanied by changes in physical contacts between droplets and other organelles. How these changes may result in improving cellular physiology, an ongoing focus in the field, is discussed.

Keywords: cellular stresses; lipid droplet assembly; metabolism; microbial invasion; starvation.

Figure 1. Steps in lipid droplet assembly

See text for details. Both seipin, involved in nascent droplet stability, and perilipin(s), which can deform membranes, have been shown to bind early in the pathway, and they may not bind in the order indicated. Maturation of junctions is considered irreversible, while both droplet release and rebinding have been postulated.

Figure 2. Lipid droplet behaviors

Schematic cartoons of droplets in yeast in ambient growth (A) and under various stresses including ER stress induced by protein mis‐folding or toxic lipid accumulation (B), and nutrient stress induced by the onset of glucose starvation (C). Long‐term nutrient deprivation can also promote vacuolar micro‐autophagy (lipophagy) of lipid droplets (D).

Figure 3. Lipid droplet interactome with other organelles

Droplets form contacts with numerous other organelles, including the endoplasmic reticulum (ER) via the protein seipin (red). Mitochondria–droplet contacts promote the transfer of fatty acids (FA) for β‐oxidation in mitochondria, and these contacts may be stabilized by perilipin 5 (Plin5, green). Similarly, in yeast peroxisome–droplet contacts are sites of FA transfer. Also in yeast, nuclear ER–vacuole junctions (NVJ) are sites of droplet budding. NVJ contact sites are maintained by the tethering proteins Nvj1p (green) and Vac8p (purple). NVJ‐associated droplets co‐localize with the NVJ tether Mdm1 (black), and the droplets are decorated with specific proteins including Prd16p (pink) and Ldo45p/16p (aqua). The PA phosphatase Pah1p (orange), which generates DAG from PA, is enriched at the NVJ periphery during the diauxic shift. NVJ‐derived droplets may be eventually digested via lipophagy at sterol‐rich microdomains at the vacuole surface in an ATG14‐dependent (gray) manner.