Redox control of enzymatic functions: The electronics of life's circuitry

Abstract

The field of redox biology has changed tremendously over the past 20 years. Formerly regarded as bi-products of the aerobic metabolism exclusively involved in tissue damage, reactive oxygen species (ROS) are now recognized as active participants of cell signaling events in health and in disease. In this sense, ROS and the more recently defined reactive nitrogen species (RNS) are, just like hormones and second messengers, acting as fundamental orchestrators of cell signaling pathways. The chemical modification of enzymes by ROS and RNS (that result in functional enzymatic alterations) accounts for a considerable fraction of the transient and persistent perturbations imposed by variations in oxidant levels. Upregulation of ROS and RNS in response to stress is a common cellular response that foments adaptation to a variety of physiologic alterations (hypoxia, hyperoxia, starvation, and cytokine production). Frequently, these are beneficial and increase the organisms' resistance against subsequent acute stress (preconditioning). Differently, the sustained ROS/RNSdependent rerouting of signaling produces irreversible alterations in cellular functioning, often leading to pathogenic events. Thus, the duration and reversibility of protein oxidations define whether complex organisms remain "electronically" healthy. Among the 20 essential amino acids, four are particularly susceptible to oxidation: cysteine, methionine, tyrosine, and tryptophan. Here, we will critically review the mechanisms, implications, and repair systems involved in the redox modifications of these residues in proteins while analyzing well-characterized prototypic examples. Occasionally, we will discuss potential consequences of amino acid oxidation and speculate on the biologic necessity for such events in the context of adaptative redox signaling.

Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase

“…These molecules have originally been seen as deleterious but in the last decade a wide array of diverse biochemical functions were assigned to them in several organisms. ROS are implicated in important basic biological processes that include cell differentiation, development and motility, cytoskeletal reorganization, cell survival and apoptosis, stress response, gut homeostasis and defense, cell signaling and transcriptional regulation [1–3]. In Drosophila melanogaster , for example, the ROS producing dual oxidase gene (DUOX) seems to play a critical role in gut innate immunity [4].…”

Identification of Surface-Exposed Protein Radicals and A Substrate Oxidation Site in A-Class Dye-Decolorizing Peroxidase from Thermomonospora curvata

“…34,35 Understanding the exact location and nature of protein radicals and their effect on the structure and function of proteins has been the subject of intense study. 36 Such examples include elucidation of roles of tyrosine and tryptophan radicals in myoglobins, cytochrome c peroxidase ( Cc P), LiP, VP, and more recently fungal DyP.…”

Mitochondria targeting by environmental stressors: Implications for redox cellular signaling

“…certain cancers) mitochondria continuously function at a higher level of ROS production. Mitochondrial biomolecules are primary targets of ROS formed within, because ROS are species that react at or near their site of formation [35, 36] . How, then, is it possible that mitochondria can function under such unfavorable conditions?…”