Abstract
Oxidative stress results from elevated levels of reactive oxygen species (ROS) in the cell and is a commonly observed consequence of high-level protein production. Gast et al. (e00301-21) show that increased levels of the ROS H2O2 in the cytosol induce a negative feedback loop reducing translation and protein production. Upon removal of the translation initiation factor kinase Gcn2, feedback inhibition is alleviated, resulting in a doubling of the recombinant protein titer. Interestingly, Gcn2 deficiency also decreased H2O2 levels, suggesting complex involvement of Gcn2 and H2O2 in coordinating cytosolic translation with endoplasmic reticulum (ER) folding.
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