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

ABSTRACT: 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 demonstrate 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.

SUBMITTER: Dr. Giuseppe Filomeni 

PROVIDER: S-SCDT-EMBOR-2020-50500V1 | biostudies-other |

REPOSITORIES: biostudies-other