Autophagy – The liaison between the lysosomal system and cell death

Hiroshi Koga, Ana Maria Cuervo

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Introduction The involvement of lysosomes, the organelle with the highest concentration of hydrolases, in cellular death has been extensively analyzed in different contexts in the past. In many of those studies, lysosomes were proposed to play a “ passive” role in the cellular death process, resulting from the leakage of potent lysosomal enzymes into the cytosol. In fact, rupture of the lysosomal membrane after various types of cellular injury or under certain pathological conditions can lead to both apoptotic and nonapoptotic cell death. For example, lysomotropic agents, certain lipid products such as sphingosine or ceramide, a wide variety of death stimuli such as death receptor activation, p53 activation, microtubule-stabilizing agents, oxidative stress, and growth factor deprivation induce lysosomal permeabilization and the release of lysosomal proteases, generically known as cathepsins, into the cytosol. Studies using both genetic and pharmacological blockage of cathepsins support that cytosolic release of these lysosomal hydrolases can mediate caspase-dependent and –independent cell death.

Original languageEnglish (US)
Title of host publicationApoptosis
Subtitle of host publicationPhysiology and Pathology
PublisherCambridge University Press
Pages63-73
Number of pages11
ISBN (Electronic)9780511976094
ISBN (Print)9780521886567
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Koga, H., & Cuervo, A. M. (2011). Autophagy – The liaison between the lysosomal system and cell death. In Apoptosis: Physiology and Pathology (pp. 63-73). Cambridge University Press. https://doi.org/10.1017/CBO9780511976094.007