Fig. 5.

The relationship among the three types of cell death. FLIP regulates the modes of cell death by interacting with caspase-8, interfering with the functions of RIPK1, and combining Atg3 and LC3 by competitively binding Atg3. Caspase-8, which is a key factor in apoptosis, inhibits necroptosis by hydrolyzing RIPK1 and RIPK3. The level of intracellular ATP plays a crucial role in the decision of cell fate between apoptosis and necrosis. High levels of intracellular ATP often favor apoptosis, whereas low levels of intracellular ATP often favor necrosis. Beclin1, which is a key molecule required for autophagosome formation, can control the switch between autophagy and apoptosis via several mechanisms, such as by combining with Bcl-2 or Bcl-XL, which are anti-apoptotic proteins, and becoming hydrolyzed by several caspase proteins. mTOR can sense the level of intracellular ATP and relieve the inhibition of autophagy when the level of intracellular ATP is low, triggering necrotic cell death. When activated by growth factor, AKT can induce mTOR signaling to inhibit autophagy. The activation of AKT can inhibit apoptosis by phosphorylating apoptotic factors, such as Bad and caspase-9