Regulation of apoptosis-associated lysosomal membrane permeabilizationReportar como inadecuado

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, Volume 15, Issue 5, pp 527–540

First Online: 14 January 2010


Lysosomal membrane permeabilization LMP occurs in response to a large variety of cell death stimuli causing release of cathepsins from the lysosomal lumen into the cytosol where they participate in apoptosis signaling. In some settings, apoptosis induction is dependent on an early release of cathepsins, while under other circumstances LMP occurs late in the cell death process and contributes to amplification of the death signal. The mechanism underlying LMP is still incompletely understood; however, a growing body of evidence suggests that LMP may be governed by several distinct mechanisms that are likely engaged in a death stimulus- and cell-type-dependent fashion. In this review, factors contributing to permeabilization of the lysosomal membrane including reactive oxygen species, lysosomal membrane lipid composition, proteases, p53, and Bcl-2 family proteins, are described. Potential mechanisms to safeguard lysosomal integrity and confer resistance to lysosome-dependent cell death are also discussed.

KeywordsLysosome Lysosomal release Caspases Calpains Hsp LAMP AbbreviationsAhrAryl hydrocarbon receptor

ANTAdenine nucleotide translocator

apoEApolipoprotein E

BH3Bcl-2 homology 3

HspHeat shock protein

JNKc-Jun N-terminal kinase

LAMPLysosome-associated membrane protein

LAPFLysosome-associated apoptosis-inducing protein containing the pleckstrin homology and FYVE domains

LEDGFLens epithelium-derived growth factor

LMPLysosomal membrane permeabilization


PLA2Phospholipase A2

ROSReactive oxygen species

siRNASmall-interfering RNA


TNFTumor necrosis factor

TRAILTumor necrosis factor-related apoptosis inducing ligand


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Autor: Ann-Charlotte Johansson - Hanna Appelqvist - Cathrine Nilsson - Katarina Kågedal - Karin Roberg - Karin Öllinger


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