Fig. 8: Model mechanism of the ROS-induced shift from apoptosis to necroptosis.
From: Mitochondrial ROS prime the hyperglycemic shift from apoptosis to necroptosis
In a hyperglycemic environment, high levels of cellular glucose lead to the production of mitochondrial ROS. Increased cellular ROS results in a decrease in the levels of executioner caspases with a concurrent increase in RIP1, RIP3, and MLKL, while also oxidizing RIP1 to a high MW oligomer. Once TNF-α engages TNFR, ROS promote formation of the necrosome and activation of RIP1, RIP3, and MLKL, while inhibiting activation of executioner caspases. In effect, the increased ROS silence apoptosis, while promoting necroptosis.
