Regulation of translation by hydrogen peroxide

Abstract

Cells must be able to maintain their intracellular homeostasis in the face of changing conditions. Typically, they respond by invoking complex regulatory mechanisms, including a global inhibition of translation. This reduction in protein synthesis may prevent continued gene expression during potentially error-prone conditions as well as allow for the turnover of existing mRNAs and proteins, whilst gene expression is directed toward the production of new molecules required to protect against or detoxify the stress. However, it is becoming increasingly recognized that not all translation is inhibited and translational control of specific mRNAs is required for survival under stress conditions. Control of protein levels via translational regulation offers a significant advantage to the cell due to the immediacy of the regulatory effect. This review describes how protein synthesis is regulated in response to oxidative stress conditions induced by exposure to hydrogen peroxide. Translational control can be mediated via direct oxidative regulation of translation factors as well via mRNA-specific regulatory mechanisms. Additionally, increasing evidence suggests that oxidative damage to the translational apparatus can itself alter the proteomic output. The resulting translational reprogramming is fundamental for adaptation to the oxidative stress. © 2011 Mary Ann Liebert, Inc.