Figure 10. A schematic model of TMZ-induced autophagy and apoptosis.

As described in detail in the text, TMZ induces ROS accumulation, mitochondrial depolarization, and MPTP opening to cause mitochondrial damage, which result in the process of protective autophagy. ETC inhibitors can reverse the above phenomena, thus enhancing TMZ-induced apoptosis. In addition, TMZ triggers ER stress with changes of GRP78, GADD153, and caspase 12 proteins. ER stress also induces autophagy through the action of JNK and intracellular calcium accumulation in glioma cells.