Transcriptional activation of lysosomal exocytosis promotes cellular clearance

Dev Cell. 2011 Sep 13;21(3):421-30. doi: 10.1016/j.devcel.2011.07.016. Epub 2011 Sep 1.


Lysosomes are cellular organelles primarily involved in degradation and recycling processes. During lysosomal exocytosis, a Ca²⁺-regulated process, lysosomes are docked to the cell surface and fuse with the plasma membrane (PM), emptying their content outside the cell. This process has an important role in secretion and PM repair. Here we show that the transcription factor EB (TFEB) regulates lysosomal exocytosis. TFEB increases the pool of lysosomes in the proximity of the PM and promotes their fusion with PM by raising intracellular Ca²⁺ levels through the activation of the lysosomal Ca²⁺ channel MCOLN1. Induction of lysosomal exocytosis by TFEB overexpression rescued pathologic storage and restored normal cellular morphology both in vitro and in vivo in lysosomal storage diseases (LSDs). Our data indicate that lysosomal exocytosis may directly modulate cellular clearance and suggest an alternative therapeutic strategy for disorders associated with intracellular storage.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • COS Cells
  • Calcium / metabolism
  • Cell Membrane / physiology
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Exocytosis / genetics*
  • HeLa Cells
  • Humans
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Membrane Fusion
  • Mice
  • Multiple Sulfatase Deficiency Disease / genetics
  • Multiple Sulfatase Deficiency Disease / metabolism
  • Multiple Sulfatase Deficiency Disease / pathology
  • TRPM Cation Channels / genetics*
  • Transcriptional Activation*
  • Transient Receptor Potential Channels
  • Up-Regulation / drug effects


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MCOLN1 protein, human
  • TFEB protein, human
  • TRPM Cation Channels
  • Transient Receptor Potential Channels
  • Calcium