Figure 3. Role of JNK in Necroptosis.

JNK promotes necroptosis through a mitochondria-dependent mechanism. Diverse cytotoxic and genotoxic stress stimuli and the activation of death receptors lead to the activation of RIP3K, which in turn potentiates and sustains the activation of JNK through MLKL as well as Ca⁺⁺-dependent mechanisms. An alternate mechanism for the sustained activation of JNK involves the inhibition of MKP1 by ROS generated by the death receptor signaling. Activated JNK promotes mitochondrial dysfunction including mitochondrial ROS generation and mitochondrial destabilization through a mechanism that remains to be clarified.