Bile acids induced necroptosis Bile acids could interact with DISC via 2 independent pathway, 1) Activate death receptors Fas and TRAIL-R2, death receptor oligomerization activate caspase 8 and FADD, this via the way to apoptosis. 2) Activate RIPK3 via FXR, this is the way to necroptosis. The caspase 8, FADD, RIPK1-RIPK3 compound determine the downstream of cell death. RIPK3 over expression will lead to cell neroptosis directly via MLKL phosphoration
Figure 2: Pathway of bile acids induced necroptosis.