Beyond indigestion: emerging roles for lysosome-based signaling in human disease. (August 2015)

• Record Type: Journal Article
• Authors: Ferguson, Shawn M
• Is Part Of: Current opinion in cell biology. Volume 35(2015)
• Page Start: 59
• Page End: 68
• Publication Date: 2015-08
• Subjects: Cells -- Periodicals; Cytology -- Periodicals; Cell Biology -- Periodicals; Biology -- Periodicals; Cells -- Periodicals; Review Literature -- Periodicals; Cell Biology; Biology; Cells; Review Literature; Cellules -- Périodiques; Cytologie -- Périodiques; Electronic journals; 571.6
• DOI: 10.1016/j.ceb.2015.04.014
• Languages: English
• ISSNs: 0955-0674

Abstract

Highlights: Lysosomes integrate multiple signals required for mTORC1 signaling. Lysosomal signals regulate gene expression through MiT-TFE transcription factors. Multiple diseases arise from mutations in lysosomal signaling protein genes. 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.