WWW.WAS.ORG • WORLD AQUACULTURE • DECEMBER 2025 67 FIGURE 1. Redox buffers stabilize cellular redox status. Simplified mechanism of redox switch regulation. Figure by Kristin Hamre. activity. Every metabolic pathway contains proteins with redox switches, and this is why redox regulation can change metabolic directions. H2O2 can be converted to water by catalase (CAT) or glutathione peroxidase (GPx), the latter under oxidation of GSH. GSSG can then be reduced back to GSH by glutathione reductase (GR). The concentration of H2O2 is partly regulated through these enzymes. The toxic hydroxyl radical (.HO) can also be formed from H2O2 through reaction with iron and copper, but the organism protects itself by binding the transition metals, for example to metallothionine, preventing accumulation of the free forms. This very short and simplified summary of redox regulation shows that the system is highly dynamic. Fish have their endogenous redox regulation, which is affected by development and growth, but at the same time, it is highly sensitive to exogenous signals. There are numerous publications showing that feed additives may cause changes in the redox system, furthermore, disease, nutrient deficiencies, hypoxia, high temperatures and handling can give oxidative or reductive stress (Phillip et al., Reviews in Aquaculture, in press). When one investigates redox regulation, it may be a challenge to differentiate between endogenous metabolism and treatment effects and to interpret biomarker responses. More research is needed to better understand this part of metabolism. It is also a challenge to measure in situ H2O2 concentrations, due to its dynamic spatiotemporal production and instability. Instead, one can measure indirect biomarkers of H2O2 metabolism as in the following experiments with Atlantic salmon. Yin, Bjornsson et al. (2022) investigated the effects of implanted growth hormone (GH) and high and low dietary vitamin C and E, on the redox biology of postsmolt Atlantic salmon. We found that It is now well known that in both plants and animals, growing tissues and growth zones generally contain more H2O2 and are more oxidized than non-growing tissues (Diebold and Chandel 2016). H2O2 is produced during mitochondrial electron transport (ETC), and by NOX enzymes, and is a key signaling molecule (Jones and Sies 2015, Sies 2017). This mechanism is believed to have evolved in parallel to photosynthesis, and increasing concentration of oxygen in the atmosphere, and arose in organisms with aerobic energy metabolism more than 2 billion years ago (Jones and Sies 2015). While concentrations of H2O2 are spatially and temporally dynamic, redox buffers, such as glutathione (GSH/GSSG, reduced/oxidized form), stabilize the redox status/ potential in cells (Figure 1). The different organelles have different redox potentials (Hamre, Zhang et al. 2024). The redox potential is in turn important for determination of the direction of metabolism. For example, the glutathione-based redox potential changes through the development of zebrafish embryos. It is reduced (low) at fertilization and becomes more oxidized (high) towards gastrulation. During organ differentiation the redox potential in the cytosol becomes more reduced, while that in mitochondria stays oxidized, underpinning the different metabolic patterns in different organelles and stages of development. It is difficult to manipulate the potential, but if you succeed, the embryos become deformed and eventually die (Hamre, Zhang et al. 2024)(Figure 2). Figure 3 shows that the first output from ETC and NOX enzymes is the superoxide anion which is converted to H2O2 by superoxide dismutase (SOD). H2O2 diffuses through membranes and reacts with redox switches in proteins, changing the protein conformation and High Growth Rate of Atlantic Salmon, Salmo salar, is Linked to Tissue Oxidation, Consumption of Antioxidants and Risk of Oxidative Stress Kristin Hamre, Peng Yin, Takaya Saito and Per Gunnar Fjelldal (CONTINUED ON PAGE 68) FIGURE 2. Developmental dynamics of glutathione redox potential in zebrafish embryos, mitochondria and cytosol. When GSSG reduction to GSH is inhibited, embryos become deformed and die before organ differentiation (Hamre, Zhang et al. 2024). Graphical abstract by Carsten Berndt.
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