Necroptosis: An emerging type of cell death in liver diseases

Figure 1 Diagrammatic representation of necroptosis pathway. Apoptosis and necroptosis can share the same death inducers molecules such as tumor necrosis factor-α (TNF-α), FasL, and TNF-related apoptosis-inducing ligand (TRAIL). The intracellular domain of TNF receptor (TNFR)1 further recruits many intracellular proteins including TNF receptor-associated death domain protein (TRADD), TNF receptor associated factor (TRAF), and receptor-interacting serine-threonine kinase 1 (RIP1). RIP1 phosphorylates and activates RIP3 which later forms the complex together with mixed lineage kinase domain-like (MLKL). C-Jun N-terminal kinase (JNK) and MLKL act downstream of RIP3. There is a possibility that some other unknown kinases might be acting between RIP1 and RIP3 which could explain why certain liver diseases do not show the protective effects of necrostatin-1.

Figure 2 Types of cell deaths. The classification shown in not generalized and is presented only for descriptional purpose. RIP: Receptor interacting proteins.