Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
- University of Cincinnati, United States
Abstract
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. 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.
Article and author information
Author details
Jeffery D Molkentin
Funding
National Institutes of Health (R01HL132831)
- Jeffery D Molkentin
Howard Hughes Medical Institute (Molkentin)
- Jeffery D Molkentin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Karch et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak
eLife 6:e30543.
https://doi.org/10.7554/eLife.30543
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