Fig. 5. mTORC1-induced activation of the ubiquitin proteasome system preserves muscle integrity.

a Representative images of Hematoxylin and eosin-stained cross sections and quantification of aberrant fibers and b representative images of tibialis anterior cross sections stained for p62 (yellow), laminin (green) and DAPI (blue) in control, TSCmKO (TSC), AKT-TG (AKT) and TSC-AKT mice after 12 days of tamoxifen treatment. c mRNA expression of ubiquitin- stress- and d autophagy-related genes in gastrocnemius muscle and e Western blots and quantification of autophagy-related protein expression in tibialis anterior muscle of control and TSCmKO mice 2 weeks after transfection of a plasmid expressing either a scrambled (Scr) or Nfe2l1-targeting (Nrf1-kd) shRNA. Des was used as the reference gene and α-actinin as the protein loading control. For a, n = 4, except for TSC-AKT where n = 3. For c–e, n = 6 per group, except for control in c, d, where n = 5. Data are presented as mean ± SEM. Two-way ANOVAs with Sidak post hoc tests were used to compare the data. *, **, and *** denote a significant difference between groups of P < 0.05, P < 0.01, and P < 0.001, respectively. For trends, where 0.05 < P < 0.10, p values are reported.