ATM plays antioxidant, boosting mitophagy via denitrosylation

• Published in: Autophagy Vol. 17; no. 2; pp. 590 - 592
• Main Authors: Cirotti, Claudia, Filomeni, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-02-2021
• Subjects: ADH5; Animals; Antioxidants - metabolism; Ataxia Telangiectasia - metabolism; Ataxia Telangiectasia Mutated Proteins - metabolism; ATM; Autophagic Punctum; Autophagy - physiology; DNA damage; GSNOR; Humans; hydrogen peroxide; mitophagy; Mitophagy - physiology; nitric oxide; oxidative stress; Reactive Oxygen Species - metabolism; S-nitrosylation; T cell; mitophagy; nitric oxide; DNA damage; T cell; S-nitrosylation; hydrogen peroxide; ATM; GSNOR; ADH5; oxidative stress
• ISSN: 1554-8627; 1554-8635
• DOI: 10.1080/15548627.2020.1860490

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.