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. Author manuscript; available in PMC: 2013 Dec 19.
Published in final edited form as: Compr Physiol. 2013 Apr;3(2):10.1002/cphy.c120020. doi: 10.1002/cphy.c120020

Figure 7.

Figure 7

Model of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced lysosomal membrane permeabilization mediated by members of the Bcl-2 family of proteins. Binding of TRAIL to death receptor 5 results in c-jun N-terminal kinase-mediated phosphorylation of Bim and its release from the cytoskeleton. At the same time, phosphofurin acidic cluster sorting protein-2 (PACS-2) associates with the internalized receptor complex in the endosomal/lysosomal compartment and then binds the cytosolic Bim, promoting Bax association to the Bim:PACS-2 complex and subsequent Bax activation. This complex has been named the PIXosome (PACS-2:BIM:BAX). After translocating to the lysosomes, Bax inserts into the membrane, homo-oligomerizes and induces lysosomal membrane permeabilization. Cathepsins are released into the cytosol where they contribute to cell death.