**14.6. What determines if autophagy is cytoprotective or cytotoxic?**

Autophagy is a process that allows cells to escape death or paradoxically leads to cell death. It is not yet understood what factors determine whether autophagy is cytoprotective or cytotoxic. It has been suggested that autophagy induced under pathological conditions functions as an adaptive cell response, allowing the cell to survive bioenergetic stress. However, autophagy is a process that destroys cellular content and organelles. In this way, it has been suggested that deregulated, excessive or persistent autophagy may lead to autophagic cell death. That is, the destruction of proteins and organelles may pass a threshold, leading to cell death. However, the point at which autophagy becomes autophagic cell death remains unclear. In this perspective, the dissection of the transition from autophagy to autophagic cell death and the cross-talking between apoptosis and autophagy may help to understand this process, leading to more efficacious treatments in cancer. In contrast, a different study has reported that when cells are subjected to prolonged growth factor deprivation or shortage of glucose and oxygen they can lose the majority of their mass via autophagy. However, when these cells are placed in optimal culture conditions, they are able to fully recover [163,213]. This result suggests that cell death via autophagy may not be simply a matter of crossing a quantitative threshold of self-digestion.
