Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease

2015 ◽  
Vol 1371 (1) ◽  
pp. 30-44 ◽  
Author(s):  
Ana Serrano-Puebla ◽  
Patricia Boya
Keyword(s):  
Cell Death ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Lysosomal Membrane Permeabilization ◽  
Health And Disease ◽  
New Evidence

scholarly journals Increased Lysosomal Membrane Permeabilization in Oxidant-exposed Macrophages of Human Fibrotic Lungs

2013 ◽  
Vol 6 ◽  
pp. JCD.S13271 ◽  
Author(s):  
Hans L Persson ◽  
Linda K. Vainikka
Keyword(s):  
Cell Death ◽  
Lung Fibrosis ◽  
Reduced Glutathione ◽  
Atomic Absorption Spectrophotometry ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Blue Staining ◽  
Green Fluorescence ◽  
Lysosomal Membrane Permeabilization ◽  
Typical Morphology

A disrupted balance of reduced glutathione (GSH) and iron (Fe) and subsequent enhanced susceptibility of lysosomes of lung macrophages (LMs) to oxidants may play a role in lung fibrogenesis. We assessed cellular Fe/GSH, lysosomal membrane permeabilization (LMP), and cell death in cultures of oxidant exposed LMs. LMs from 7 lung fibrosis patients and healthy subjects were exposed to a physiologic concentration of H2O2 for 1 h. LMP was assessed with acridine orange green fluorescence, apoptosis/necrosis were estimated by apoptotic DNA and typical morphology, Fe was assessed with Prussian blue staining/atomic absorption spectrophotometry, and GSH was evaluated using a GSH assay kit. Oxidant-induced LMP and cell death were more pronounced in cultures of LMs from patients with lung fibrosis, and these cells contained less GSH and more cytochemically stained Fe. These observations indicate that LMP may be involved in fibrosis development, possibly through activation of the inflammasome complex. Further studies are warranted for a detailed understanding.

Lysosomes in programmed cell death pathways: from initiators to amplifiers

2017 ◽  
Vol 398 (3) ◽  
pp. 289-301 ◽  
Author(s):  
Nežka Kavčič ◽  
Katarina Pegan ◽  
Boris Turk
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Inflammasome Activation ◽  
Biological Macromolecules ◽  
Lysosomal Hydrolases ◽  
Lysosomal Membrane Permeabilization ◽  
Cell Death Pathways ◽  
Major Attention

Abstract Lysosome is the central organelle for intracellular degradation of biological macromolecules and organelles. The material destined for degradation enters the lysosomes primarily via endocytosis, autophagy and phagocytosis, and is degraded through the concerted action of more than 50 lysosomal hydrolases. However, lysosomes are also linked with numerous other processes, including cell death, inflammasome activation and immune response, as well as with lysosomal secretion and cholesterol recycling. Among them programmed cell death pathways including apoptosis have received major attention. In most of these pathways, cell death was accompanied by lysosomal membrane permeabilization and release of lysosomal constituents with an involvement of lysosomal hydrolases, including the cathepsins. However, it is less clear, whether lysosomal membrane permeabilization is really critical for the initiation of cell death programme(s). Therefore, the role of lysosomal membrane permeabilization in various programmed cell death pathways is reviewed, as well as the mechanisms leading to it.

GDC-0941 enhances the lysosomal compartment via TFEB and primes glioblastoma cells to lysosomal membrane permeabilization and cell death

2013 ◽  
Vol 329 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Stefanie Enzenmüller ◽  
Patrick Gonzalez ◽  
Georg Karpel-Massler ◽  
Klaus-Michael Debatin ◽  
Simone Fulda
Keyword(s):  
Cell Death ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Glioblastoma Cells ◽  
Lysosomal Compartment ◽  
Lysosomal Membrane Permeabilization

scholarly journals Lysosomal Membrane Permeabilization Induces Cell Death in a Mitochondrion-dependent Fashion

2003 ◽  
Vol 197 (10) ◽  
pp. 1323-1334 ◽  
Author(s):  
Patricia Boya ◽  
Karine Andreau ◽  
Delphine Poncet ◽  
Naoufal Zamzami ◽  
Jean-Luc Perfettini ◽  
...  
Keyword(s):  
Cell Death ◽  
Uv Light ◽  
Chromatin Condensation ◽  
Cell Loss ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Cytotoxic Action ◽  
Double Knockout ◽  
Lysosomal Membrane Permeabilization ◽  
Mitochondrial Membrane Permeabilization

A number of diseases are due to lysosomal destabilization, which results in damaging cell loss. To investigate the mechanisms of lysosomal cell death, we characterized the cytotoxic action of two widely used quinolone antibiotics: ciprofloxacin (CPX) or norfloxacin (NFX). CPX or NFX plus UV light (NFX*) induce lysosomal membrane permeabilization (LMP), as detected by the release of cathepsins from lysosomes. Inhibition of the lysosomal accumulation of CPX or NFX suppresses their capacity to induce LMP and to kill cells. CPX- or NFX-triggered LMP results in caspase-independent cell death, with hallmarks of apoptosis such as chromatin condensation and phosphatidylserine exposure on the plasma membrane. LMP triggers mitochondrial membrane permeabilization (MMP), as detected by the release of cytochrome c. Both CPX and NFX* cause Bax and Bak to adopt their apoptotic conformation and to insert into mitochondrial membranes. Bax−/− Bak−/− double knockout cells fail to undergo MMP and cell death in response to CPX- or NFX-induced LMP. The single knockout of Bax or Bak (but not Bid) or the transfection-enforced expression of mitochondrion-targeted (but not endoplasmic reticulum–targeted) Bcl-2 conferred protection against CPX (but not NFX*)-induced MMP and death. Altogether, our data indicate that mitochondria are indispensable for cell death initiated by lysosomal destabilization.

scholarly journals DRAM Triggers Lysosomal Membrane Permeabilization and Cell Death in CD4+ T Cells Infected with HIV

2013 ◽  
Vol 9 (5) ◽  
pp. e1003328 ◽  
Author(s):  
Mireille Laforge ◽  
Sophie Limou ◽  
Francis Harper ◽  
Nicoletta Casartelli ◽  
Vasco Rodrigues ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Cd4 T Cells ◽  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Lysosomal Membrane Permeabilization
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