Fig. 9.

Schematic figure showing that melatonin attenuates mechanical trauma-induced hepatic injury by inhibiting IP₃R1-mediated MAMs formation via activating the melatonin receptor-ERK1/2-FoxO1 pathway. Melatonin binds to melatonin receptor and induces the phosphorylation of ERK1/2 that subsequently interacts with FoxO1 and induces the phosphorylation and inactivation of the FoxO1. Inactivated FoxO1 reduced FoxO1 binding to the IP₃R1 promoter to inhibit IP₃R1-mediated MAMs. Subsequently, melatonin-induced downregulation of IP₃R1 inhibits MAMs formation and Ca²⁺ overload, and mitigates mitochondrial dysfunction and mechanical trauma-induced hepatic injury