Figure 6
From: Fine-tuning of AMPK–ULK1–mTORC1 regulatory triangle is crucial for autophagy oscillation
An extra element in the AMPK-P–ULK1-P negative feedback loop results in an oscillatory characteristic both in starvation and rapamycin treatment. The effect of delayed AMPK-P → AMPK substrate → ULK1-P ┤ AMPK-P negative feedback loop was systematically analysed upon various stress events. The balance curves of ULK1-P (green curve) and AMPK-P (orange curve) are plotted (upper panel). The phaseplanes are shown for (a) physiological conditions (b) starvation (STARV = 0.5) and (c) rapamycin treatment (mTORT = 0.3). Trajectories are depicted with black lines, while stable and unstable steady states are visualized with black and white dots, respectively. The computational simulations (lower panel) are determined upon (a) physiological conditions (b) starvation (STARV = 0.5) and (c) rapamycin treatment (mTORT = 0.3). The relative activity of mTORC1, AMPK-P, ULK1-P, PROT (AMPK substrate) and autophagy activator complex (ATG) is shown.
