Figure 7.

Mechanism diagram for the role of Ripk3-AMPK-Drp1-mPTP in LPS-mediated acute lung injury via initiating necroptosis. LPS injury caused upregulation of Ripk3, which resulted in a reduction in the phosphorylation of AMPK. Inactivating AMPK hindered the phosphorylation of Drp1 at Ser637, which triggered fatal mitochondrial fission. Excessive fission caused the opening of mPTP, ultimately leading to the necroptosis of PMVECs. Nevertheless, the recovery of AMPK activity could halt the excessive fission, offering prosurvival effects for the lung in the presence of LPS injury. Our findings revealed a novel role for Ripk3 in LPS-induced acute lung injury through regulating Drp1-mediated mitochondrial fission via the AMPK signaling pathway. These results suggest that targeting Ripk3 could be a promising therapeutic approach for treating acute lung injury in clinical practice.