ATM plays antioxidant, boosting mitophagy via denitrosylation

Abstract

Mitophagy is a selective process aimed at removing damaged or burned-out mitochondria; it is activated upon different stimuli and plays a fundamental role in preventing overproduction of reactive oxygen species (ROS) that might be generated by dysfunctional mitochondria. From this angle, mitophagy can be considered a fully-fledged antioxidant process. Such a surrogate antioxidant function is recently emerging, being shared among many molecular pathways and players that are usually not included among–and, formally, do not directly act as–antioxidants. ATM (ataxia telangiectasia mutated) is a prototype of this class of “neglected” antioxidants. In spite of its well-known role in DNA damage response, many phenotypes of ataxia telangiectasia (A-T) patients are, indeed, related to chronic oxidative stress, arguing for an additional antioxidant role of ATM. In a recent study, we discovered the mechanism through which ATM exerts antioxidant activity. In particular, we provided evidence that this involves ADH5/GSNOR (alcohol dehydrogenase 5 (class III), chi polypeptide), which, in turn, sustains mitophagy via PARK2 denitrosylation, and protects the cell from detrimental effects due to ROS.