Fig. 7: Endonuclease activity of ENDOG is essential for autophagy induction.

a Schematic diagram of human wild-type ENDOG and ENDOG mutations. Del-1–48, deletion of the N-terminal 48 amino acids; EM, endonuclease activity mutation by mutagenized H-N-N motif (141H/163 N/172N) to 141A/163 A/172A; ENDOG-NLS, replacement of the mitochondrial targeting sequence with a nuclear localization signal sequence. b, c Western blots (b) and quantitative results (c) of the indicated proteins in ENDOG knockout L02 cells following overexpression of wild-type or mutant ENDOG and starved for 6 h (n = 3 independent samples; data are presented as mean values ± SD, *p < 0.05; **p < 0.01, ***p < 0.001). d, e Representative images (d) and respective quantitative results (e) of mCherry-GFP-LC3 puncta in the indicated cell groups under starvation and CQ treatments (WT: wild-type L02 cells; KO: ENDOG knockout L02 cells; plasmids transiently transfected for 48 h; starvation for 6 h; CQ: 50 μM for 6 h; scale bar = 10 μm; n = 100 independent cells examined over three independent experiments; data are presented as mean values ± SD, **p < 0.01, ***p < 0.001). f Model depicting ENDOG promotes autophagy through its phosphorylation-mediated interaction with 14-3-3γ and its endonuclease activity-mediated DNA damage response. Source data are provided as a Source data file.