Fig. 5: Inhibition of mitochondrial protein synthesis leads to early activation of OMA1-mediated ISR.
From: Mitoribosomal synthetic lethality overcomes multidrug resistance in MYC-driven neuroblastoma
a–d Western blotting detection and densitometric analysis of markers of mitochondrial stress, ISR and stress signaling kinases in a panel of neuroblastoma cells after DOXY treatment for 24 h (a, b) and over a 16-h time course (c, d). Normalized protein levels are plotted relative to untreated controls, mean ± SD. Treatment with 0.1 µM thapsigargin for 1 h served as a positive control of PERK phosphorylation, assessed by a reduced electrophoretic mobility in 6% polyacrylamide gel. Western blotting and densitometric analysis of YME1L1 after 24-h DOXY treatment and densitometric analysis of p-p38 MAPK (T180/Y182)/p38 MAPK during 16-h DOXY treatment are provided in Fig. S6b, c, respectively. Statistical significance was determined by one-way ANOVA followed by Tukey’s multiple comparisons test (b, d), *p < 0.05, **p < 0.01, ***p < 0.001, #p < 0.0001.
