Oxidation as a Post-Translational Modification that Regulates Autophagy

The toxicity associated with accumulation of reactive oxygen species (ROS) has led to the evolution of various defense strategies to overcome oxidative stress, including autophagy. This pathway is involved in the removal and degradation of damaged mitochondria and oxidized proteins. At low levels, however, ROS act as signal transducers in various intracellular pathways. In a recent study we described the role of ROS as signaling molecules in starvation-induced autophagy. We showed that starvation stimulates formation of ROS, specifically H2O2, in the mitochondria. Furthermore, we identified the cysteine protease HsAtg4 as a direct target for oxidation by H2O2, and specified a cysteine residue located near the HsAtg4 catalytic site as critical for this regulation. Here we focus on Atg4, the target of regulation, and discuss possible mechanisms for the regulation of this enzyme in the autophagic process.Addendum to:Reactive Oxygen Species Are Essential for Autophagy and Specifically Regulate the Activity of Atg4R. Scherz-Shouval, E. Shvets, E. Fass, H. Shorer, L. Gil and Z. ElazarEMBO J 2007; doi: 10.1038/sj.emboj.7601623