Dynamic Modelling of Pathways to Cellular Senescence Reveals Strategies for Targeted Interventions
Figure 3
mTOR inhibition decreased mitochondrial mass.
(A) Simulated time-courses for mitochondrial mass. Gradual mTOR specific inhibition from 0% (black, control) to 90% predicted a decrease in mitochondrial mass due to the perturbation of the population of old mitochondria. (B) The model prediction was confirmed by measuring mitochondrial mass using mitotracker green and quantifying the fluorescence intensities (n = 3). Exogenous addition of 10 nM Torin1 significantly decreased the average mass (Mann-Whitney test, * P<0.05) in vitro. In silico inhibition of mTOR levels also partially decreased mitochondrial mass in a dose dependent manner, with between 15 and 30% levels giving equivalent restoration of ψm to the in vitro data. (C) Example images of data used in (B) for control cells (upper panel) and cells treated with Torin in the medium (lower panel) for 15 days post IR, stained with the mitochondrial ψm dependent dye TMRM, the non-potential dependent dye mitotracker green, and the nuclear counterstain Hoechst 33342. Scale bar is 10 µm.
