The pROS of autophagy in neuronal health

Autophagy refers to a set of catabolic pathways that together facilitate degradation of superfluous, damaged and toxic cellular components. The most studied type of autophagy, called macroautophagy, involves membrane mobilisation, cargo engulfment and trafficking of the newly formed autophagic vesicle to the recycling organelle, the lysosome. Macroautophagy responds to a variety of intra- and extra-cellular stress conditions including, but not limited to, pathogen intrusion, oxygen or nutrient starvation, proteotoxic and organelle stress, and elevation of reactive oxygen species (ROS). ROS are highly reactive oxygen molecules that can interact with cellular macromolecules (proteins, lipids, nucleic acids) to either modify their activity or, when released in excess, inflict irreversible damage. Although increased ROS release has long been recognised for its involvement in macroautophagy activation, the underlying mechanisms and the wider impact of ROS-mediated macroautophagy stimulation remain incompletely understood.