Fig. 4: TRIM21 depletion facilitates VDAC2 oligomerization-mediated mtDNA release.

a–d The indicated NPC cells were treated with IR. The relative MTATP8 abundance in the cytosolic fractions was assessed by qPCR (a). Cytosolic mtDNA accumulation was evaluated by quantification of cytoplasmic TFAM (indicated by the white arrows) 24 h after IR treatment. Representative images (scale bar, 10 μm) and quantitative results are shown (n = 30 cells per group) (b). The levels of total and phosphorylated STING, TBK1, IRF3 and STAT1 (c) and the IFN-β1 level in culture supernatants (d) were measured 48 h after IR treatment. e Co-IP with an anti-FLAG antibody revealed the enhanced interaction of two exogenous VDAC2 monomers in lysates of irradiated NPC cells. f Immunoblot analysis showed an increased level of VDAC2 oligomers in NPC cells 24 h after IR treatment. g VDAC2 oligomers in WT and TRIM21-KO NPC cells 24 h after IR treatment. h–j NPC cells were pre-treated with the VDAC2 oligomerization inhibitor DIDS (100 μM) or DMSO for 24 h and were then treated with IR. The relative cytosolic MTATP8 abundance was assessed by qPCR 24 h after IR treatment (h). The levels of phosphorylated STING, TBK1, IRF3 and STAT1 (i), as well as the expression levels of IFNB1, CCL5, and CXCL10 (j), were measured 48 h after IR treatment. n = 3 independent experiments. The data are presented as the mean ± SEM (a, b, d, h and j). Comparisons were performed using one-way ANOVA with the Tukey’s test for multiple comparisons.