# Cell Response to Oxidative Stress in Antarctic Filamentous Fungi
## 4 ROS and Oxidative Stress  
### ROS: Origin, Sources, Damages  
The designation ROS denotes a collective term of oxygen-containing reactive species that are formed during the process of incomplete oxygen reduction. They include superoxide radicals (\({}^{\bullet}\)O\({}_{2}\)\({}^{-}\)), hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), hydroxyl radicals (OH\(\bullet\)), singlet oxygen (\({}^{1}\)O\({}_{2}\)), peroxyl radical (LOO\({}^{\bullet}\)), alkoxyl radical (LO\({}^{\bullet}\)), lipid hydroperoxide (LOOH), peroxynitrite (ONOO\(-\)), hypochlorous acid (HOCI), and ozone (O\({}_{3}\)), among others [92]. Some of ROS contain one or more unpaired electrons, which are called oxygen radicals or oxygen free radicals, for example \({}^{\bullet}\)O\({}_{2}\)\({}^{-}\), OH\(\bullet\), LOO\({}^{\bullet}\), and LO\({}^{\bullet}\). The ROS that do not contain any unpaired electrons, such as H\({}_{2}\)O\({}_{2}\), HOCI, and O\({}_{3}\), are not free radicals [93; 94]. ROS are inevitable by-products of the normal aerobic metabolism of cells. The mitochondrial respiratory chain is the major source of ROS. Under normal oxy conditions, only 1-2% of total oxygen is converted into free radicals [95]. The primary species \({}^{\bullet}\)O\({}_{2}\)\({}^{-}\), H\({}_{2}\)O\({}_{2}\), and HO\(\bullet\) are the result of successive processes of monovalent O\({}_{2}\) reduction [Figure 1]. The initial monovalent reduction results in the formation of \({}^{\bullet}\)O\({}_{2}\)\({}^{-}\), which is subsequently followed by the reduction of a second electron, leading to the release of H\({}_{2}\)O\({}_{2}\). \({}^{\bullet}\)O\({}_{2}\)\({}^{-}\) also reacts with H\({}_{2}\)O\({}_{2}\) to generate HO\(\bullet\) (Haber-Weiss reaction) [96]. The superoxide  
Figure 1: Mechanisms of ROS generation. radical is most commonly produced in mitochondria. It has a very short lifetime and relatively low reactivity. \({}^{\bullet}\)O\({}_{2}\)\({}^{-}\) does not react with most biological molecules. Its chemical activity depends on where it is produced in the cell, its ability to be protonated to a more powerful oxidant (peroxyl radical), and its collision with a suitable substrate [97]. Hydrogen peroxide is an unstable and slowly decaying molecule containing an oxygen-oxygen bond. The main source of H\({}_{2}\)O\({}_{2}\) is the superoxide radical dismututation reaction or the two-electron reduction of oxygen in reactions catalyzed by xanthine oxidase, glucose oxidase, and others. The H\({}_{2}\)O\({}_{2}\) molecule is uncharged and can cross biological membranes. It is a powerful oxidant, but the kinetics of its reaction with biomolecules are quite slow, leading to its accumulation in cells at relatively high concentrations [98]. The hydroxyl radical is one of the most reactive radicals present in biological systems and has a relatively short half-life (10\({}^{-8}\) to 10\({}^{-9}\) s) [99]. It exhibits a direct effect near its point of origin, without making long transitions into the living cell, causing damage to the first molecule it encounters. Singlet oxygen is a non-radical form of oxygen. It is an oxygen molecule in which one of the two free electrons is in an excited state. Thus, \({}^{1}\)O\({}_{2}\) can transfer energy to other molecules and act as a catalyst for the formation of free radicals. ROS can originate from both external sources and intracellular processes. Their formation occurs across a variety of biochemical and physiological functions [94]. Besides the mitochondrial electron transport chain, various cellular organelles, including peroxisomes, lysosomes, the endoplasmic reticulum, etc., which depend on oxygen for their activities, also contribute to the intracellular reservoir of ROS. A range of enzymes such as NADPH oxidases, xanthine oxidase, cyclooxygenase, lipoxygenase, and other free ions (such as iron and copper) has been associated with the generation of ROS. The group of exogenous sources includes ultraviolet radiation, polycyclic aromatic hydrocarbons (PAHs), \(\gamma\)-irradiation, and environmental pollution.