Fig. 4.

Calcium and reactive oxygen species (ROS) as primary drivers of JNK-dependent necrotic cell death. In this model, calcium and reactive oxygen species (ROS) are involved in an amplification cycle leading to cell death. Calcium overload in the mitochondria causes ROS generation, ROS can in turn increase intracellular calcium by directly activating calcium channels or increasing membrane permeability by lipid peroxidation and inactivating calcium removal transporters, JNK inhibitors break this cycle to attenuate the increase in both ROS and calcium.