Beyond indigestion: emerging roles for lysosome-based signaling in human disease

Curr Opin Cell Biol. 2015 Aug;35:59-68. doi: 10.1016/ Epub 2015 May 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • GTP Phosphohydrolases / metabolism
  • Homeostasis
  • Humans
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism


  • Multiprotein Complexes
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • GTP Phosphohydrolases