%0 Figure %A Dalle Pezze, Piero %A Nelson, Glyn %A G. Otten, Elsje %A I. Korolchuk, Viktor %A B. L. Kirkwood, Thomas %A von Zglinicki, Thomas %A P. Shanley, Daryl %D 2014 %T Combined mTOR-ROS inhibition increased mitochondrial membrane potential. %U https://plos.figshare.com/articles/figure/_Combined_mTOR_ROS_inhibition_increased_mitochondrial_membrane_potential_/1154717 %R 10.1371/journal.pcbi.1003728.g004 %2 https://ndownloader.figshare.com/files/1653923 %K oxidative stress response %K senescence onset %K cell cycle arrest %K FoxO 3a transcription factors %K ros %K Systems Biology Approach %K mitochondrial mass changes %K Mitochondrial membrane %K time points %K Reactive oxygen species %K mitochondrial mass %K DNA damage %K mitochondrial fission %K network stabilised %K cellular senescence %K Dynamic Modelling %K Dynamic sensitivity analysis %K feedback pathways %K Targeted Interventions Cellular senescence %K networked system %K model predictions %K whilst inhibition %K Dual inhibition %K mitochondrial regulation %K network sensitivity %X

(A) Model predictions were obtained by plotting the intensity for each readout (membrane potential (ψm), mitochondrial mass and DNA damage, respectively) with inhibition of mTOR (x axis) and ROS (y axis). The control (no inhibition) is represented as the point (0, 0). Prediction data are shown at days 12, 15, 18 and 21 post-irradiation. (B) In vitro ψm, mitochondrial mass and DNA damage foci number upon inhibition of ROS, TOR or combined TOR-ROS at days 12, 15, 18 and 21, or 18 and 21 (for DNA damage foci). Cells were treated with 10 nM Torin1 (TOR inhibitor), or Torin1 with SOD and catalase (100 U each) (n = 3, ANOVA with Dunn's post-hoc test, * P<0.05 within time points). (C) Example images of data used in (B) for control cells (left panels) and cells treated with Torin1, SOD and catalase in the medium (right panel) stained for ψm and mitochondrial mass at day 21 (above panel) or for DNA damage foci at day 18 (lower panel).

%I PLOS Computational Biology