Fig. 3. SIFI silences the mitochondrial stress response.

a, UBR4 deletion amplifies ISR signalling after arsenite (5 μM, 16 h) or CCCP (10 μM, 8 h) treatment, as detected by flow cytometry of uORF-ATF4-gated GFP translation. Upper schematic: map of ISR activation reporter, which measures uORF-gated translation of GFP controlled by IRES-mCherry. Similar results in n ≥ 2 independent experiments. b, WT and ΔUBR4 cells were treated with CCCP (16 h) and ATF4 was detected by western blotting. Similar results in n = 2 independent experiments. c, Western blot of WT and ΔUBR4 cells depleted of TIMM8A treated with arsenite (5 μM, 16 h). Similar results in n = 2 independent experiments. d, RNA-seq analysis of WT, ΔUBR4, WT sgTIMM8A, ΔUBR4 sgTIMM8A and arsenite-treated WT and ΔUBR4 cells. e, WT and ΔUBR4 cells were treated with arsenite (5 μM), and ATF4 was monitored by western blotting. Quantification of n = 4 independent experiments. Data shown as the mean ± s.e.m. f, WT and ΔUBR4 cells were depleted of CReP, treated with arsenite (5 μM) and analysed by western blotting. Similar results in n = 4 independent experiments. For gel source data, see Supplementary Fig. 1.