Fig. 5.

Contribution of autophagy to either cell survival or cell death. Basal ROS levels contribute to cell signaling and also basal autophagy, necessary to maintain protein turnover and proteostasis. A, under mild oxidative stress conditions, redox-mediated signaling and/or oxidative modification of macromolecules may up-regulate the autophagy flux in order to eliminate non-functional and potentially damaging cellular structures, including aggregates and affected organelles. In this context, autophagy would also exert a pro-survival function. B, the contribution of the lysosomal system to either cell survival or cell death depends on a tightly regulated equilibrium of ROS and autophagy. C, under chronic or massive oxidative stress circumstances, lysosomes could negatively contribute to cell fate as a source of ROS, leakage of proteases into the cytosol, degradation of essential cellular components and eventually leading to autophagy cell death. D, the bi-phasic autophagy response to stress. In the first phase there is a rapid increase in the autophagy flux that is mediated by post-translational protein modifications. This response may be followed by a delayed and extended phase that relies on the activation of specific transcriptional programs including NRF2, NFκB, p53 or FoxO3.