Figure 7

Schematic illustrates how USP18 deficiency regulated mtDNA release in DENV infection. After DENV infection, sequential events occurred in the mitochondria, and some events were enhanced in response to USP18 deficiency. USP18 deficiency resulted in several events, including the enhancement of production of mtROS, calcium mobilization to mitochondria, suppression of OGG1 expression, generation of oxidized mtDNA, formation of mtDNA fragments and opening of mPTP-VDAC pores in DENV infection. These events resulted in the release of oxidized and fragmented mtDNA from mitochondria to the cytosol to activate the downstream signaling pathways. WT, wild-type; ROS, reactive oxygen species; mPTP, mitochondrial permeability transition pore; mtDNA, mitochondrial DNA; OGG1, 8-oxoguanine DNA glycosylase 1; CsA, cyclosporin A; VBIT-4, a voltage-dependent anion channel (VDAC) oligomerization inhibitor. The figure was generated using BioRender.