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