Figure 3.

ROS induce cell death, mainly including apoptosis, necroptosis and ferroptosis. (Ⅰ) Exceeding ROS promote both the extrinsic and intrinsic apoptosis pathway: ROS activate extrinsic apoptosis pathway by accelerating the ubiquitin degradation of c-FLIP, then enhancing the binding between the adaptor protein and pro-caspase-8; ROS induce intrinsic apoptosis by facilitating the release of Cyt-c from mitochondria to cytoplasm to form apoptosome with casp-9 and APAF-1. (Ⅱ) ROS and necroptosis form a positive feedback loop: ROS stabilize RIP3 protein to lead to the formation of DISC Ⅱb (necrosome); in turn, RIP3 can facilitate the TCA cycle and aerobic respiration in mitochondria to induce ROS generation. (Ⅲ) Ferroptosis is a ROS-dependent form of RCD: the basic of ferroptosis is GSH anabolism disorder leads to the lethal accumulation of PUFAs peroxidation; p53 plays opposite roles on ROS and ferroptosis by inhibiting SLC7A11 expression or increasing NADPH production.