Fig. 7: The ISR caused by mtDNA mutation burden regulates UPRmt activation.

a Protein expression of HSP60, LONP1, and ClpP by western blot analysis in the intestinal crypts in WT/WT*, WT/Mut**, and Mut/Mut*** mice at 8 months of age. Relative band densities quantified using ImageJ are shown at bottom (Data are presented as the mean ± S.D and n = 3 mice per group; one-way ANOVA test). b Protein expression of LONP1 by western blot analysis in the intestinal crypts of Mut/Mut*** mice treated with ISRIB or control. Relative band densities quantified using ImageJ are shown on right (Data are presented as the mean ± S.D and n = 3 mice per group; paired two-tailed Student’s t-test). c Protein expression of LONP1 by western blot analysis in the intestinal crypts of Mut/Mut*** mice treated with siAtf5 or siNC. Relative band densities quantified using ImageJ are shown on right (Data are presented as the mean ± S.D and n = 2 mice per group; paired two-tailed Student’s t-test). d Summary of mechanism regulating intestinal aging caused by mtDNA mutation burden. The figures of small intestine and mitochondria were generated with the help of Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 4.0 unported license (https://creativecommons.org/licenses/by/4.0/deed.en).