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Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
by
Karch, Jason
, Schips, Tobias G
, Sargent, Michelle A
, Brody, Matthew J
, Molkentin, Jeffery D
, Maliken, Bryan D
, Kanisicak, Onur
in
Amino acids
/ Animals
/ Apoptosis
/ Autophagy
/ bcl-2 Homologous Antagonist-Killer Protein - deficiency
/ bcl-2 Homologous Antagonist-Killer Protein - metabolism
/ Bcl-2 protein
/ bcl-2-Associated X Protein - deficiency
/ bcl-2-Associated X Protein - metabolism
/ Biochemistry
/ Cell death
/ Cell Membrane - metabolism
/ Cells, Cultured
/ Detergents
/ Developmental Biology
/ Embryo fibroblasts
/ Embryos
/ Fibroblasts
/ Fibroblasts - physiology
/ Gangrene
/ Gene Deletion
/ Lysosomes - metabolism
/ Medical research
/ Membrane permeability
/ Mice
/ Mitochondria
/ Necrosis
/ Null cells
/ Organelles
/ Permeability
/ Phagocytosis
/ Research Advance
/ Scientific equipment industry
/ Statistical analysis
2017
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Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
by
Karch, Jason
, Schips, Tobias G
, Sargent, Michelle A
, Brody, Matthew J
, Molkentin, Jeffery D
, Maliken, Bryan D
, Kanisicak, Onur
in
Amino acids
/ Animals
/ Apoptosis
/ Autophagy
/ bcl-2 Homologous Antagonist-Killer Protein - deficiency
/ bcl-2 Homologous Antagonist-Killer Protein - metabolism
/ Bcl-2 protein
/ bcl-2-Associated X Protein - deficiency
/ bcl-2-Associated X Protein - metabolism
/ Biochemistry
/ Cell death
/ Cell Membrane - metabolism
/ Cells, Cultured
/ Detergents
/ Developmental Biology
/ Embryo fibroblasts
/ Embryos
/ Fibroblasts
/ Fibroblasts - physiology
/ Gangrene
/ Gene Deletion
/ Lysosomes - metabolism
/ Medical research
/ Membrane permeability
/ Mice
/ Mitochondria
/ Necrosis
/ Null cells
/ Organelles
/ Permeability
/ Phagocytosis
/ Research Advance
/ Scientific equipment industry
/ Statistical analysis
2017
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Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
by
Karch, Jason
, Schips, Tobias G
, Sargent, Michelle A
, Brody, Matthew J
, Molkentin, Jeffery D
, Maliken, Bryan D
, Kanisicak, Onur
in
Amino acids
/ Animals
/ Apoptosis
/ Autophagy
/ bcl-2 Homologous Antagonist-Killer Protein - deficiency
/ bcl-2 Homologous Antagonist-Killer Protein - metabolism
/ Bcl-2 protein
/ bcl-2-Associated X Protein - deficiency
/ bcl-2-Associated X Protein - metabolism
/ Biochemistry
/ Cell death
/ Cell Membrane - metabolism
/ Cells, Cultured
/ Detergents
/ Developmental Biology
/ Embryo fibroblasts
/ Embryos
/ Fibroblasts
/ Fibroblasts - physiology
/ Gangrene
/ Gene Deletion
/ Lysosomes - metabolism
/ Medical research
/ Membrane permeability
/ Mice
/ Mitochondria
/ Necrosis
/ Null cells
/ Organelles
/ Permeability
/ Phagocytosis
/ Research Advance
/ Scientific equipment industry
/ Statistical analysis
2017
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Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
Journal Article
Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
2017
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Overview
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.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
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