Fig. 3: Doxorubicin-induced necroptosis.
From: Regulated cell death pathways in doxorubicin-induced cardiotoxicity
Schematic representation of the doxorubicin-induced necroptosis pathway. Doxorubicin causes upregulation of TNFα, activating TRADD and FADD, and upon caspase 8 inhibition and activation of RIPK1, RIPK3, and MLKL induces cell death via necroptosis. Doxorubicin can also activate necroptosis via the RIPK1 independent pathway, where RIPK3 activates CAMKII and mitochondrial permeability transition pore (mPTP) resulting in membrane potential and integrity loss. TNFα tumor necrosis factor-alpha, TRADD tumor necrosis factor receptor type 1 associated death domain protein, FADD Fas-associated protein with death domain, RIPK receptor-interacting serine/threonine-protein kinase, CAMKII calcium/calmodulin-dependent protein kinase II association domain, MLKL mixed lineage kinase domain-like, mPTP mitochondrial permeability transition pore.
