# Cell Response to Oxidative Stress in Antarctic Filamentous Fungi
## 4 ROS and Oxidative Stress
### ROS: Origin, Sources, Damages
Exposure to different drugs like cisplatin, doxorubicin, paclitaxel, metformin, atorvastatin, and others can also cause an increase in the ROS level. Under normal conditions, the level of radicals is adequate to the level of the cell's defense system, and they manage to maintain an oxidation-reduction equilibrium; i.e., a balance is observed between the formation and elimination of ROS. However, the over-production of ROS can exceed the protective mechanisms of cells, leading to detrimental impacts on cellular elements such as lipids, proteins, and nucleic acids [97] [Figure 2]. Carbohydrates, albeit to a lesser degree, are also affected by ROS [100]. Although DNA is a stable, well-protected molecule, ROS can interact with it and cause various types of damage. In the human body, such processes have been shown to occur at a rate of 104 lesions per cell per day. ROS damages the DNA molecule by removing an electron from it and turning it into an unstable molecule. Mitochondrial and chloroplast DNA are more susceptible to oxidative damage than nuclear DNA due to the lack of protective proteins and histones and their proximity to ROS-producing systems. ROS has been demonstrated to induce a series of molecular events, including binding to DNA bases or deoxyribose, DNA chain breakage, removal of nucleotides, modifications in nucleotides, and subsequent mutations. Additionally, covalent binding to a protein molecule has been observed as a result of ROS action (Figure 3) [97; 101; 102]. Proteins are also susceptible to biological oxidation due to their prevalence in cells and their high rate of constant interaction with numerous types of free radicals. Consequently, protein damage is a significant consequence of free radical formation within and outside the cell. ROS can cause hydrogen removal, electron transfer (oxidation or reduction), addition, fragmentation and rearrangement reactions, dimerization, disproportionation, and substitution in amino acids, peptides, and proteins, etc. (Figure 4) [100; 103; 104]. Figure 4: Oxidative-induced damage of proteins. Figure 3: Changes in DNA as a result of oxidative damage. Figure 2: Oxidative damage to intracellular molecules. Oxidative effects on lipids play a particularly important role in cell biology, human health, and the food industry. In cells, a process called lipid peroxidation takes place in which free radicals attack lipids (particularly polyunsaturated fatty acids, PUFAs), removing hydrogen while incorporating oxygen. Responsible for this process are hydroxyl radicals (OH\(\bullet\)), which are mainly formed by the Fenton [Reaction 1] and Haber-Weiss [Reaction 2] reactions [10]. Theoretically, the Haber-Weiss reaction cannot play a major role in vivo because its rate constant is lower than that of the dismutation reaction. However, the Fenton reaction, which exploits the ability of iron ions to participate in redox-cyclic interactions and increases the rate of the process, is much more feasible. Lipid peroxidation is considered to be a major molecular mechanism involved in oxidative damage to all structures that can lead to cell death [105,106]. Cell membranes and membranes of subcellular organelles composed of polyunsaturated fatty acids are the first targets of radical attack. These include mitochondrial membranes, microsomes, peroxisomes, and cytoplasmic membranes. Glycolipids, phospholipids, and cholesterol are also damaged or fatally modified by lipid peroxidation (Figure 5).