Death-associated protein kinase (DAPK) and signal transduction: fine-tuning of autophagy in Caenorhabditis elegans homeostasis

Autophagy is an evolutionarily conserved lysosomal pathway used to degrade and recycle long-lived proteins and cytoplasmic organelles. This homeostatic ability makes autophagy an important pro-survival mechanism in response to several stresses, such as nutrient starvation, hypoxia, damaged mitochondria, protein aggregation and pathogens. However, several recent studies have highlighted that autophagy also acts as a pro-death mechanism. What on the surface seem like conflicting roles of autophagy may be explained by the fact that the decision between pro-survival and pro-death is determined by the level of activation. A better understanding of autophagy signaling pathways will be helpful to elucidate how the level of autophagy is precisely regulated under different conditions and eventually how the final outcome is decided. In this review, we briefly discuss the pro-survival and pro-death roles of autophagy, and then discuss the mechanism by which autophagy is regulated, mainly focusing on death-associated protein kinase in the nematode Caenorhabditis elegans.