Research ArticleCELL STRESS

Mitochondrial redox sensing by the kinase ATM maintains cellular antioxidant capacity

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Science Signaling  10 Jul 2018:
Vol. 11, Issue 538, eaaq0702
DOI: 10.1126/scisignal.aaq0702

Antioxidant role of ATM

The kinase ATM is integral to repairing damaged DNA. Hence, its loss has severe consequences for the development of disease. However, ATM also separately functions in the response to reactive oxygen species (ROS). ROS cause oxidative stress, a classic feature of cells in patients with the neurodegenerative disease ataxia telangiectasia (A-T), for which ATM was named. Using a mutant that impairs only the ROS-responsive function of ATM, Zhang et al. found that ROS produced by the mitochondria trigger the dimerization of ATM, which indirectly increased the expression and activity of an enzyme that shifts glucose flux from glycolysis and lactic acid production to the pentose phosphate pathway (PPP) and NADPH production, thereby increasing the antioxidant capacity of cells. These findings show how loss of the ROS-sensing, antioxidant function of ATM may contribute to the phenotypes of A-T.

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