Figure 1.
The formation of reduced oxygen species (ROS) and the main types of damage these molecules produce within cells. (A) The mitochondria are a predominant source for ROS production when electrons (e−) escape from complexes I, II, and III, and will quickly react with oxygen (O2) to produce superoxide anion (O2•−). Superoxide dismutase (SOD) will reduce O2•− to hydrogen peroxide (H2O2), where it can enter the cytoplasm through peroxiporins in the mitochondrial membrane. In the cytoplasm, H2O2 can further react with transition metals, such as iron (Fe2+), to produce the hydroxyl radical (•OH) and hydroxide (OH−). Nitric oxide synthase (NOS) will generate nitric oxide (NO) in normal amino acid metabolism. However, reactive nitrogen species (RNS) may also be produced from O2•− reacting with NO to produce peroxynitrite (ONOO−). The endoplasmic reticulum (ER) is also responsible for producing ROS from excess protein synthesis that can lead to misfolded proteins and ER stress. Stressed ER will generate H2O2. (B) Nucleic acids, lipids, and proteins are primary targets for ROS-induced damage. Nucleic acid damage forms lesions and strand breaks in DNA and can alter the methylation profile. Lipid peroxidation of the cell, mitochondria, and nucleus are another target for ROS. Damage occurs when •OH binds to lipids to generate a peroxyl radical that will react with an additional polyunsaturated fatty acid to form hydroperoxide and alkyl radicals (ROO•). This feed-forward reaction will compromise membrane fluidity and function. Additionally, mitochondrial membrane permeability may be altered to change the conductance state of the mitochondria. Protein damage is also caused by ROS where •OH binds to generate ROO•. Created with Biorender.com (accessed on 12 January 2023).