Figure 5.

Redox-mediated regulated cell death (apoptosis and necroptosis) in hepatocytes. TNF-α/FasL induces primarily redox-dependent apoptosis via a caspase 8/3 pathway. When caspase 8 is not available/inactivated, the alternative pathway is activated to form a necrosome (MLKL/RIP1/RIP3) to induce necroptosis, also in a redox-dependent manner. Necroptosis occurs as “a backup for apoptosis” at a later phase. Reactive oxygen species (ROS; e.g., H₂O₂) primarily induce apoptosis and, thereafter, necroptosis in the presence of MLKL. The induction of necroptosis by H/R is affected by the reexpression of RIP1, RIP3, and MLKL after reoxygenation but is independent of caspase activity. The precise molecular mechanisms are still unknown, but oxidative stress definitely plays a pivotal role in liver injury via regulated cell death.