The membrane-snipping protein Dynamin 2 enables cells to burn fat by spurring the formation of new lysosomes, Schulze et al. show.
Many kinds of cells cache lipid droplets that they can consume when nutrients are scarce. One way that cells break down these droplets is through autophagy. A membrane pocket in the cytoplasm encircles a droplet and then merges with a lysosome, forming a structure called an autolysosome that digests the lipids. Autolysosomes sprout buds that detach and mature into fresh lysosomes ready for another delivery of lipids. During endocytosis, the GTPase Dynamin 2 snips free newly formed vesicles. Schulze et al. asked whether the protein performs a similar function during the production of replacement lysosomes.
Knocking down or inhibiting Dynamin 2 suppressed the breakdown of lipid droplets in liver cells, the team found. Lysosomes ballooned to 4–5 times their normal size and sprouted long membranous tubules.
When Schulze et al. dosed liver cells with a Dynamin 2 inhibitor and then removed the compound, some of the tubules that extended from autolysosomes began to fragment. This result suggests that Dynamin 2 helps midwife new lysosomes by cutting them loose from their parental autolysosome. The researchers now want to determine whether Dynamin 2 carries out the same task in other cell types that are reliant on lipid droplets, such as muscle cells and adipocytes.
Text by Mitch Leslie