Fig. 6
From: Research progress on multiple cell death pathways of podocytes in diabetic kidney disease
Necroptosis-related pathway. Necroptosis can be engaged by the ligation of TNF receptor family proteins (including TNFR, FAS, TRAILR, and DR6) through RIPK1–RIPK3 when Caspase-8 activity is blocked. Necroptosis can be also triggered by the activation of TLR3 and TLR4 by double stranded RNA (dsRNA) and LPS in macrophages, respectively, through TRIF-dependent activation of RIPK3. Viral RNA and the released DNA/RNA from damaged mitochondria can induce necroptosis by ZBP1-dependent activation of RIPK3. Activated RIPK3 phosphorylates MLKL and leads to the subsequent oligomerization of MLKL. The oligomerized MLKL translocates to the plasma membrane and engages ion channels and mediates plasma membrane rupture