Computing direction

JCB • VOLUME 175 • NUMBER 1 • 2006 4 R egeneration after liver damage requires caveolin and lipid droplets, according to Manuel Fernández, Cecilia Albor (Universitat de Barcelona, Spain), Albert Pol, Robert Parton (University of Queensland, Brisbane, Australia), and colleagues. The results suggest that caveolin helps process or package storage lipids, and that the system somehow communicates with the cell cycle machinery. Caveolin is best known as an essential component of ordered plasma membrane domains called caveolae. Besides overseeing signaling and sorting in caveolae, caveolin has also been seen around lipid droplets after partial hepatectomy. These lipid droplets have a core of storage lipids surrounded by a single monolayer of phospholipids. They are thought to bud from the ER membrane after forming between its two leafl ets. In partially hepatectomized mice lacking caveolin, the group found that initial events were intact: the two main signaling pathways that initiate recovery were activated, and levels of fatty acids increased in the serum and inside cells. But then things deteriorated. The signaling pathways persisted longer than normal, and lipid droplet accumulation and a marker of cell cycle progression were greatly reduced. The outcome was approximately half as much liver regeneration, and eightfold more death. Glucose feeding rescued these cell cycle and survival defects. The glucose may be acting by providing an alternate source of energy, membrane lipids, or both. Lipid droplet formation and caveolin’s involvement in it remain a mystery. Perhaps caveolin helps package lipids in a way that allows them to be used properly. The group is now interested in seeing which stages of lipid droplet formation and lipid metabolism are blocked in the mutants, and in teasing apart the link from lipid metabolism to cell cycle.