Birt-Hogg-Dubé syndrome and the lysosomal sensing of intracellular nutrients

Birt-Hogg-Dubé syndrome is a human disease that is characterized by numerous benign hair follicle tumors, the growth of pulmonary cysts that confer a high risk for collapsed lungs (pneumothorax) and a very high incidence of kidney cancer (renal carcinoma). We became interested in Birt-Hogg-Dubé syndrome and FLCN due to the possibility of links between the renal carcinoma that arises in this disease and reports of renal carcinoma (and other cancers) that arise in humans due to mutations that increase the expression and/or activity of MiT/TFE transcription factors. Following up on this line of reasoning, we have identified a novel lysosome-localized function for FLCN in coupling the sensing of nutrient availability to MiT/TFE regulation. Having identified the critical role for FLCN in coupling nutrient sensing to regulation of lysosome-dependent signaling, we are continuing to investigate both the specific mechanisms that underlie such regulation as well as the contributions of dysregulation of this process to Birt-Hogg-Dubé syndrome. For more details, please refer to the following publication from our lab: Petit et al, Journal of Cell Biology, 2013.