Rare genetic disorders such as Pompe disease result from the functional failure of lysosomes. These cellular organelles break down and recycle unwanted molecules, then fuse with the cell membrane to expel their contents. When the process fails, waste accumulates in cells.

Andrea Ballabio at the Telethon Institute of Genetics and Medicine in Naples, Italy, and his colleagues report that the TFEB protein that regulates lysosomes' formation and function also regulates lysosomal dumping. Moreover, overexpressing this protein reverses some of the pathologies associated with lysosomal storage diseases.

The authors boosted TFEB expression in human cells and observed them with electron microscopy. More lysosomes clustered at the cell membrane, and levels of calcium ions — needed for the organelles to fuse with the membrane — were higher than normal.

In cellular models of lysosomal diseases, overexpressing TFEB enhanced the organelles' ability to clear waste products and the cells regained their normal morphology. Delivering the Tfeb gene to mouse models decreased signs of cell death.

Dev. Cell 10.1016/j.devcel.2011.07.016 (2011)