Elucidation of fundamental mechanisms controlling lysosome homeostasis

Recognizing that lysosomes perform multiple essential functions for cells, we reasoned that cells must have the ability to sense the status of their lysosomes and to adjust the activity of their lysosomes to match ongoing changes in demand. In search of molecular mechanisms that mediate such regulation, we identified the MiT/TFE family of transcription factors (TFEB, TFE3 and MITF) as proteins that shuttle between lysosomes and the nucleus so as to couple changes in lysosome status to the regulation of gene expression. We are continuing to investigate the mechanisms whereby changes within the inside of lysosomes are sensed and communicated to the rest of the cell. More details on this topic can be found in the following publication: Roczniak-Ferguson et al, Science Signaling, 2012.