Figure 6. Decreasing Tim17A/TIM-17 Increases Expression of Stress-Responsive Mitochondrial Proteostasis Genes and Confers Stress-Resistance in C. elegans and Mammalian Cells.
A. Representative images depicting the activation of the UPRmt reporter hsp-60pr::gfp in C. elegans strains fed E. coli expressing empty vector (EV), tim-17(RNAi) or tim-23(RNAi), as indicated. The strains used in this figure are N2 (wild-type; top), haf-1(ok705) (middle), and atfs-1(tm4525) (bottom).
B. qPCR of HSP60 and YME1L in HEK293T cells stably-expressing control or TIM17A shRNA. mRNA levels were normalized to GAPDH. The error bars show the mean +/− 95% confidence interval. Data are representative of 3 independent experiments.
C. Survival analysis of N2 worms fed E. coli expressing empty vector (EV; black), tim-17(RNAi) (red) or tim-23(RNAi) (blue). Animals were treated with the indicated concentration of paraquat at Day 1 of adulthood. Animal survival was scored following a 24 h paraquat treatment. Error bars show SEM for n=8. Data are representative of 4 independent experiments.
D. Survival analysis of atfs-1(tm4525) mutant worms fed E. coli expressing empty vector (EV; black), tim- 17(RNAi) (red) or tim-23(RNAi) (blue). Animals were treated with the indicated concentration of paraquat at Day 1 of adulthood. Animal survival was scored following a 24 h paraquat treatment. Error bars show SEM for n=8. Data are representative of 4 independent experiments.
E. Bar graph showing the resazurin fluorescence of HEK293T cells expressing control or TIM17A shRNA and treated with the indicated concentration of paraquat for 24h. Error bars show SEM for n=8. Data are representative of 3 independent experiments.
**indicates p-value < 0.01, ***indicates p-value < 0.005.
see also Figure S5