A universally conserved ATPase regulates the oxidative stress response in Escherichia coli
08.11.2012
Wenk M, Ba Q, Erichsen V, Macinnes K, Wiese H, Warscheid B, Koch HG.
J Biol Chem. 2012;287(52):43585-98
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 tumours. 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 employed Escherichia coli as model organism and found that YchF over-expression 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 a H2O2-dependent de-phosphorylation. 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 cells ability to scavenge damaging reactive oxygen species.
