| First Author | Karch J | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 29148970 | Mgi Jnum | J:254971 |
| Mgi Id | MGI:6110945 | Doi | 10.7554/eLife.30543 |
| Citation | Karch J, et al. (2017) Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. Elife 6:e30543 |
| abstractText | 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. |
