From the integrated stress response to oxidative stress: A historical perspective

Oxidative stress has exerted fundamental evolutionary pressure since the emergence of aerobic life. Its impact on the physiology and function of all organisms is profound and consequential for cell survival. The integrated stress response (ISR) plays a critical role in counteracting oxidative stress via translational control of a subset of mRNAs. Here, we summarize the fundamental discoveries that shaped our understanding of the ISR pathway's role in cellular adaptation to oxidative stress from studies of protein synthesis in reticulocyte lysates to the regulation of glutathione metabolism downstream of the ISR pathway. We describe recent advances in studying mRNA translation changes in response to oxidative stress based on high throughput translatome analyses.