Lysosomal signaling controls cell homeostasis

A Ballabio

Telethon Institute of Genetics and Medicine (TIGEM) and Medical Genetics, Department of Translational Medicine, Federico II University, Naples, Italy, Department of Molecular and Human Genetics, Baylor College of Medicine and Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, TX, USA

In the early 50s, Christian De Duve identified a new cellular structure, the lysosome, defined as the cell’s "suicide bag". Sixty years later, it is clear that the lysosome greatly exceeded the expectations of its discoverer. Over 50 different types of lysosomal storage diseases have been identified, each due to the deficiency or malfunction of a specific lysosomal protein. In addition, an important role of the lysosome has been unveiled in several common human diseases, such as cancer, obesity, neurodegenerative diseases, and infection. Recent studies in our lab have led to the identification of a lysosome-to-nucleus signaling pathway and a lysosomal gene network that regulate cellular clearance and energy metabolism. These observations have changed our traditional view of the lysosome from a dead-end organelle and last step of cell catabolism to a signaling hub that controls cellular energy metabolism. An important challenge for the future will be to exploit these discoveries to identify modulators of lysosomal function that may be used to treat human diseases.