Abstract
Cells must be able to respond and adapt to different stress conditions to maintain normal function. A common response to stress is the global inhibition of protein synthesis. Protein synthesis is an expensive process consuming much of the cell’s energy. Consequently, it must be tightly regulated to conserve resources. One of these stress conditions is oxidative stress, resulting from the accumulation of reactive oxygen species (ROS) mainly produced by the mitochondria but also by other intracellular sources. Cells utilize a variety of antioxidant systems to protect against ROS, directing signaling and adaptation responses at lower levels and/or detoxification as levels increase to preclude the accumulation of damage. In this review, we focus on the role of hydrogen peroxide, H2O2, as a signaling molecule regulating protein synthesis at different levels, including transcription and various parts of the translation process, e.g., initiation, elongation, termination and ribosome recycling.
Highlights
All eukaryotic organisms utilize oxygen-dependent metabolism because, through evolution, this molecule has been selected as a final electron acceptor in respiration in most cases
reactive oxygen species (ROS) can act as a second messenger involved in signaling pathways and produce beneficial effects, a phenomenon called mitohormesis, as originally observed using moderate levels of the redox-cycling drug paraquat, acting in mitochondria to increase the levels of ROS [10]
As an example of ROS acting as a signaling molecule, we have shown that light is converted by a peroxisomal oxidase into an H2 O2 signal that is sensed by the yeast peroxiredoxin Tsa1 to inhibit protein kinase A (PKA)-dependent phosphorylation of the yeast general stress-responsive Zn finger transcription factor Msn2 [11]
Summary
All eukaryotic organisms utilize oxygen-dependent metabolism because, through evolution, this molecule has been selected as a final electron acceptor in respiration in most cases. ROS can act as a second messenger involved in signaling pathways and produce beneficial effects (e.g., support health and longevity), a phenomenon called mitohormesis, as originally observed using moderate levels of the redox-cycling drug paraquat, acting in mitochondria to increase the levels of ROS [10]. In their recent review, Sies et al described two new concepts, oxidative eustress for the beneficial effects of H2 O2 and O2 − and oxidative distress for the irreversible damage that can result from higher levels of H2 O2 and O2 − [3,9]. This review describes the role of H2 O2 in the different stages of protein synthesis, from transcription to translation, focusing on the role of H2 O2 as a signaling molecule
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