Fig. 1: Major molecular mechanisms of different types of regulated cell death.

A In apoptosis, the intrinsic pathway is mainly mediated by mitochondria. TNFα can stimulate the extrinsic pathway and induce apoptosis (left). If caspase-8 activity is inhibited, RIPK1 forms necrosomes with RIPK3 and MLKL, thereby triggering necroptosis (right). B Autophagy begins with the formation of phagophores. This process is regulated by ULKL and Beclin-1. The ATG12-ATG5-ATG16L1 complex and LC3-II recruit loads to cargo receptors, which is essential for the process of phagophore expansion to generate autophagosomes. C In the classical pyroptosis pathway, when cells are exposed to external stimuli, activated caspase-1 can cleave GSDMD to produce an N-terminal of GSDMD, which can form holes in the cell membrane to release mature IL-1β and IL-18 and induce pyroptosis. In the non-classical pyroptosis pathway, GSDMD is cleaved by caspase-4, -5, and -11. Pyroptosis can also trigger the release of HMGB1 and K⁺. D Iron accumulation and lipid peroxidation are important factors that trigger reactive oxygen species (ROS) production and ferroptosis. The ACSL4-LPCAT3-ALOXs pathway enables the production of phospholipid hydroperoxide (PLOOH) from polyunsaturated fatty acids (PUFAs), which is oxidized from fatty acids. In the most studied antioxidant system, the Xc-system-GSH-GPX4, GPX4 can scavenger oxygen free radicals and inhibit ferroptosis. Other antioxidant systems, such as CoQ10-AIFM2 and ESCRT-III membrane repair systems, also play important roles in inhibiting lipid peroxidation.