Lysosomal pathways to cell death and their therapeutic applications

Exp Cell Res. 2012 Jul 1;318(11):1245-51. doi: 10.1016/j.yexcr.2012.03.005. Epub 2012 Mar 15.


Lysosomes are the major cell digestive organelles that were discovered over 50 years ago. They contain a number of hydrolases that help them to degrade intracellular and extracellular material delivered. Among the hydrolases, the cathepsins, a group of proteases enclosed in the lysosomes, have a major role. About a decade ago, the cathepsins were found to participate in apoptosis. Following their release into the cytosol, they cleave Bid and degrade antiapoptotic Bcl-2 proteins, thereby triggering the mitochondrial pathway of apoptosis, with the lysosomal membrane permeabilization being the critical step in this pathway. Lysosomal dysfunction is linked with several diseases, including cancer and neurodegenerative disorders, thereby providing a potential for therapeutic applications. In this review lysosomes and lysosomal proteases involvement in apoptosis and their possible pharmaceutical targeting are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents
  • Apoptosis*
  • Cathepsins / metabolism
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / enzymology
  • Lysosomes / metabolism*
  • Peptide Hydrolases / drug effects


  • Antineoplastic Agents
  • Cathepsins
  • Peptide Hydrolases