Figure 4. Functional relationship between autophagy and apoptosis.

a | Hypothetical scenario of an absent interplay between autophagy and apoptosis. If no functional connection between apoptosis and autophagy existed, the percentage of cells activating the autophagic pathway or instead succumbing to apoptosis would be solely determined by stress intensity over time. b | Effect of cytoprotective autophagy on a dose-response curve. If autophagy inhibits apoptosis, the cell population becomes relatively resistant to cell death, unless the intensity of the stressor overcomes the protective barrier of autophagy. c | Cytoprotective autophagy, followed by lethal subversion of the apoptotic machinery. In this scenario, autophagy would constitute an initial barrier against apoptosis when stress intensity is low (1). As stress intensity increases (2), the induction of apoptosis results in the subversion of cytoprotective mechanisms, including autophagy, and the conversion of cytoprotective molecules into cytotoxic ones. For example, cleavage of essential ATG proteins does not only inactivate the autophagic machinery but also leads to the generation of protein fragments with novel pro-apoptotic properties.