Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.14016
Title: Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway
Authors: Leow S.M. 
Serene Chua S.X. 
Venkatachalam G. 
Shen L. 
Luo L. 
Clement M.-V. 
Keywords: caspase 3
cathepsin
gelsolin
hydrogen peroxide
lamin A
lamin C
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
transcription factor
transcription factor EB
unclassified drug
basic helix loop helix leucine zipper transcription factor
caspase 3
cathepsin
hydrogen peroxide
oxidizing agent
TFEB protein, rat
animal cell
apoptosis
Article
Atg9b gene
biogenesis
cell count
cell membrane permeability
cell nucleus
concentration (parameters)
controlled study
Ctsb gene
Ctsl gene
cytosol
enzyme activation
enzyme substrate
gene
gene expression
gene silencing
genetic variability
intracellular transport
Lamp2 gene
Lamp2a gene
lysosome membrane
Neu1 gene
nonhuman
oxidative stress
phenotype
protein cleavage
protein function
protein transport
rat
RNA splicing
signal transduction
Sqstm1 gene
animal
cell line
cell membrane permeability
cell survival
confocal microscopy
cytology
drug effects
genetics
immunoblotting
intracellular membrane
lysosome
metabolism
myoblast
nucleocytoplasmic transport
reverse transcription polymerase chain reaction
RNA interference
Active Transport, Cell Nucleus
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Caspase 3
Cathepsins
Cell Line
Cell Membrane Permeability
Cell Survival
Gene Expression
Hydrogen Peroxide
Immunoblotting
Intracellular Membranes
Lysosomes
Microscopy, Confocal
Myoblasts
Oxidants
Oxidative Stress
Rats
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Signal Transduction
Issue Date: 2017
Citation: Leow S.M., Serene Chua S.X., Venkatachalam G., Shen L., Luo L., Clement M.-V. (2017). Sub-lethal oxidative stress induces lysosome biogenesis via a lysosomal membrane permeabilization-cathepsin-caspase 3-transcription factor EB-dependent pathway. Oncotarget 8 (10) : 16170-16189. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.14016
Abstract: Here we provide evidence to link sub-lethal oxidative stress to lysosome biogenesis. Exposure of cells to sub-lethal concentrations of exogenously added hydrogen peroxide resulted in cytosol to nuclear translocation of the Transcription Factor EB (TFEB), the master controller of lysosome biogenesis and function. Nuclear translocation of TFEB was dependent upon the activation of a cathepsin-caspase 3 signaling pathway, downstream of lysosomal membrane permeabilization and accompanied by a significant increase in lysosome numbers as well as induction of TFEB-dependent lysosome-associated genes expression such as Ctsl, Lamp2 and its spliced variant Lamp2a, Neu1, Ctsb, Sqstm1, and Atg9b. The effects of sublethal oxidative stress on lysosomal gene expression and biogenesis were rescued upon gene silencing of caspase 3 and TFEB. Notably, caspase 3 activation was not associated with phenotypic hallmarks of apoptosis, evidenced by the absence of caspase 3 substrate cleavage, such as PARP, Lamin A/C or gelsolin. Taken together, these data demonstrate for the first time an unexpected and non-canonical role of a cathepsin-caspase 3 axis in the nuclear translocation of TFEB leading to lysosome biogenesis under conditions of sub-lethal oxidative stress.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/173806
ISSN: 19492553
DOI: 10.18632/oncotarget.14016
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