scholarly journals Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jason Karch ◽  
Tobias G Schips ◽  
Bryan D Maliken ◽  
Matthew J Brody ◽  
Michelle A Sargent ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Permeability ◽  
Apoptotic Cell ◽  
Lysosomal Membrane ◽  
Autophagic Cell Death ◽  
Mutant Form ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Intracellular Organelles ◽  
Cellular Necrosis

Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and previous we have shown that these two effectors are also needed for mitochondrial-dependent cellular necrosis (Karch et al., 2013). Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells. Moreover, a monomeric-only mutant form of Bax is sufficient to increase lysosomal membrane permeability and restore autophagic cell death in Bax/Bak1 double-deleted mouse embryonic fibroblasts. Finally, increasing lysosomal permeability through a lysomotropic detergent in cells devoid of Bax/Bak1 restores autophagic cell death, collectively indicting that Bax/Bak integrate all major forms of cell death through direct effects on membrane permeability of multiple intracellular organelles.

scholarly journals STF-62247 and pimozide induce autophagy and autophagic cell death in mouse embryonic fibroblasts

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maximilian N. Kinzler ◽  
Svenja Zielke ◽  
Simon Kardo ◽  
Nina Meyer ◽  
Donat Kögel ◽  
...  
Keyword(s):  
Cell Death ◽  
Autophagic Cell Death ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts

scholarly journals Author response: Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak

2017 ◽  
Author(s):  
Jason Karch ◽  
Tobias G Schips ◽  
Bryan D Maliken ◽  
Matthew J Brody ◽  
Michelle A Sargent ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Permeability ◽  
Lysosomal Membrane ◽  
Autophagic Cell Death ◽  
Author Response

scholarly journals The Loss of HIF1αLeads to Increased Susceptibility to Cadmium-Chloride-Induced Toxicity in Mouse Embryonic Fibroblasts

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Ajith Vengellur ◽  
Elizabeth Grier ◽  
John J. LaPres
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Protective Role ◽  
Activity Levels ◽  
Wild Type ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Cadmium Treatment ◽  
Increased Susceptibility

Wild-type and HIF1α −/− MEF cells were used to determine the role of HIF1α in cadmium-induced toxicity. Cadmium treatment did not affect HIF1-mediated transcription but led to caspase activation and apoptotic cell death in wild-type and HIF1α −/− cells. Cadmium-induced cell death, however, was significantly higher in HIF1α −/− cells as compared to their wild-type counterparts. Increased cell death in the HIF1α −/− cells was correlated with lower metallothionein protein, elevated levels of reactive oxygen species, and decreased superoxide dismutase enzyme activity. The total and oxidized glutathione levels, and, correspondingly, lipid peroxidation levels were elevated in the null cells compared to wild-type cells, indicating increased antioxidant demand and greater oxidative stress. Overall, the results suggest that basal levels of HIF1α play a protective role against cadmium-induced cytotoxicity in mouse embryonic fibroblasts by maintaining metallothionein and antioxidant activity levels.

scholarly journals Chloroquine induces lysosomal membrane permeability mediated apoptotic cell death in bladder cancer cells

2016 ◽  
Vol 27 (2) ◽  
pp. S5 ◽  
Author(s):  
Hung-En Chen ◽  
Ji-Fan Lin ◽  
Te-Fu Tsai ◽  
Yi-Chia Lin ◽  
Kuang-Yu Chou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Membrane Permeability ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Lysosomal Membrane ◽  
Bladder Cancer Cells

Enniatin B1-induced lysosomal membrane permeabilization in mouse embryonic fibroblasts

2019 ◽  
Vol 36 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Carlos A. F. Oliveira ◽  
Lada Ivanova ◽  
Anita Solhaug ◽  
Christiane K. Fæste
Keyword(s):  
Membrane Permeabilization ◽  
Lysosomal Membrane ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Lysosomal Membrane Permeabilization

scholarly journals Caspase3-deficient cells require fibronectin for protection against autophagy-dependent death

2021 ◽  
Author(s):  
David B. Weir ◽  
Lawrence H. Boise
Keyword(s):  
Cell Death ◽  
Survival Advantage ◽  
Deficient Mouse ◽  
Wild Type ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Serum Withdrawal ◽  
Presence And Absence ◽  
Induced Apoptosis

ABSTRACTCaspases are required for execution of apoptosis. However, in their absence, signals that typically induce apoptosis can still result in cell death. Our laboratory previously demonstrated that Casp3-deficient mouse embryonic fibroblasts (MEFs) have increased fibronectin (FN) secretion, and an adhesion-dependent survival advantage compared to wild type (WT) MEFs. Here, we show that FN is required for survival of Casp3-deficient MEFs following serum withdrawal. Furthermore, when FN is silenced, serum withdrawal-induced death is caspase-independent. However, procaspase-7 is cleaved, suggesting that MOMP is taking place. Indeed, in the absence of FN, cytochrome c release is increased following serum withdrawal in Casp3-deficient MEFs. Yet death does not correspond to cytochrome c release in Casp3-deficient MEFs. This is true both in the presence and absence of FN. Additionally, caspase-independent death is inhibited by Bcl-XL overexpression. These findings suggest that Bcl-XL is not inhibiting death through regulation of Bax/Bak insertion into the mitochondria, but through a different mechanism. One such possibility is autophagy and induction of autophagy is associated with caspase-independent death in Casp3-deficient cells. Importantly, when ATG5 is ablated in Casp3-deficient cells, autophagy is blocked and death is largely inhibited. Taken together, our data indicate that Casp3-deficient cells incapable of undergoing canonical serum withdrawal-induced apoptosis, are protected from autophagy-dependent death by FN-mediated adhesion.

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