A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli*

M. Wenk,Qiaorui Ba,Veronika Erichsen,K. MacInnes,Heike Wiese,B. Warscheid,H. Koch

Published 2012 in Journal of Biological Chemistry

ABSTRACT

Background: YchF is a universally conserved ATPase of unknown function. Results: YchF inhibits catalase activity, and high YchF levels cause H2O2 hypersensitivity. YchF is negatively regulated by OxyR in response to H2O2. Conclusion: YchF is a universally conserved negative regulator of the oxidative stress response that acts by a post-translational mechanism. Significance: This is the first functional description of the YchF protein family. YchF is an evolutionarily conserved ATPase of unknown function. In humans, the YchF homologue hOla1 appears to influence cell proliferation and was found to be up-regulated in many tumors. A possible involvement in regulating the oxidative stress response was also suggested, but details on the underlying mechanism are lacking. For gaining insight into YchF function, we used Escherichia coli as a model organism and found that YchF overexpression resulted in H2O2 hypersensitivity. This was not caused by transcriptional or translational down-regulation of H2O2-scavenging enzymes. Instead, we observed YchF-dependent inhibition of catalase activity and a direct interaction with the major E. coli catalase KatG. KatG inhibition was dependent on the ATPase activity of YchF and was regulated by post-translational modifications, most likely including an H2O2-dependent dephosphorylation. We furthermore showed that YchF expression is repressed by the transcription factor OxyR and further post-translationally modified in response to H2O2. In summary, our data show that YchF functions as a novel negative regulator of the oxidative stress response in E. coli. Considering the available data on hOla1, YchF/Ola1 most likely execute similar functions in bacteria and humans, and their up-regulation inhibits the ability of the cells to scavenge damaging reactive oxygen species.

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