Redox activation of ATM enhances GSNOR translation to sustain mitophagy and tolerance to oxidative stress

Claudia Cirotti, Salvatore Rizza, Paola Giglio, Noemi Poerio, Maria Francesca Allega, Giuseppina Claps, Chiara Pecorari, Ji Hoon Lee, Barbara Benassi, Daniela Barilà, Caroline Robert, Jonathan S. Stamler, Francesco Cecconi, Maurizio Fraziano, Tanya T. Paull, Giuseppe Filomeni

Research output: Contribution to journalArticlepeer-review


The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide and mitochondrial ROS. The use of selective pharmacological inhibitors and siRNA demonstrates that GSNOR induction is an event downstream of the redox-mediated activation of ATM, which in turn phosphorylates and activates CHK2 and p53 as intermediate players of this signaling cascade. The modulation of ATM/GSNOR axis, or the expression of a redox-insensitive ATM mutant influences cell sensitivity to nitrosative and oxidative stress, impairs mitophagy and affects cell survival. Remarkably, this interplay modulates T-cell activation, supporting the conclusion that GSNOR is a key molecular effector of the antioxidant function of ATM and providing new clues to comprehend the pleiotropic effects of ATM in the context of immune function.

Original languageEnglish
JournalEMBO Reports
Publication statusE-pub ahead of print - Nov 2020


  • ATM
  • mitophagy
  • ROS
  • T cell

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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