DisseCCTing phospholipid function in lipid droplet dynamics

Abstract

Phospholipids provide an amphipathic barrier between lipid droplets and the cytoplasm of cells. In this issue of Cell Metabolism, Krahmer and colleagues (2011) define a role for phosphatidylcholine in preventing lipid droplet coalescence and show that the rate-limiting enzyme in phosphatidylcholine synthesis is activated through binding to lipid droplets.

Figure 1. Phosphatidylcholine synthesis and lipid droplet dynamics

Dietary choline is taken up across the plasma membrane (PM) and is phosphorylated by choline kinase (CK). Phosphocholine is converted to CDP-choline by CTP:phosphocholine cytidylyltransferase (CCT), which binds to endoplasmic reticulum (ER) membranes and the phospholipid monolayer (colored blocks) of lipid droplets (LD) via an amphipathic helical domain (Krahmer, et al, 2011); membrane binding activates the enzyme. CDP-choline is condensed with diglyceride (DG) to make phosphatidylcholine (PC) by an integral protein of the ER membrane, CDP-choline:1,2 diacylglycerol cholinephosphotransferase (CPT). Phosphatidylcholine (represented by red blocks) is the most abundant phospholipid in cellular membranes and the phospholipid monolayer of lipid droplets. Lipid droplets are thought to originate as a lens of triglyceride (TG) within the membrane bilayer of the ER. Following expansion of the triglyceride core, lipid droplets bud out of the ER to become independent organelles in the cytoplasm of the cell. When phosphatidylcholine is limiting in the phospholipid monolayer coating the lipid droplet (Inset), adjacent lipid droplets coalesce into larger lipid droplets (Krahmer, et al., 2011). Lipid droplet-associated proteins may also promote lipid droplet fusion; candidates include SNAP23, and Fsp27/CIDEC. (Illustration by R. Hasney)