title: Beyond indigestion: emerging roles for lysosome-based signaling in human disease.
abstract: Lysosomes are becoming increasingly recognized as a hub that integrates diverse signals in order to control multiple aspects of cell physiology. This is illustrated by the discovery of a growing number of lysosome-localized proteins that respond to changes in growth factor and nutrient availability to regulate mTORC1 signaling as well as the identification of MiT/TFE transcription factors (MITF, TFEB and TFE3) as proteins that shuttle between lysosomes and the nucleus to elicit a transcriptional response to ongoing changes in lysosome status. These findings have been paralleled by advances in human genetics that connect mutations in genes involved in lysosomal signaling to a broad range of human illnesses ranging from cancer to neurological disease. This review summarizes these new discoveries at the interface between lysosome cell biology and human disease.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, United States; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510, United States. Electronic address: shawn.ferguson@yale.edu.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020558:GTP Phosphohydrolases