Autophagy Signaling Through Reactive Oxygen Species

Autophagy is a degradative pathway that involves delivery of cytoplasmic components, including proteins, organelles, and invaded microbes to the lysosome for digestion. Autophagy is implicated in the pathology of various human diseases. The association of autophagy to inflammatory bowel diseases is consistent with recent discoveries of its role in immunity. A complex of signaling pathways control the induction of autophagy in different cellular contexts. Reactive oxygen species (ROS) are highly reactive oxygen free radicals or non-radical molecules that are generated by multiple mechanisms in cells, with the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria as major cellular sources. These ROS are important signaling molecules that regulate many signal-transduction pathways and play critical roles in cell survival, death, and immune defenses. ROS were recently shown to activate starvation-induced autophagy, antibacterial autophagy, and autophagic cell death. Current findings implicate ROS in the regulation of autophagy through distinct mechanisms, depending on cell types and stimulation conditions. Conversely, autophagy can also suppress ROS production. Understanding the mechanisms behind ROS-induced autophagy will provide significant therapeutic implications for related diseases. Antioxid. Redox Signal. 14, 2215-2231.