Reactive Oxygen Species (ROS)
Chemically reactive molecules containing oxygen (including superoxide, hydrogen peroxide, and hydroxyl radicals) that can damage DNA, proteins, and cell membranes. ROS are generated during normal metabolism and inflammation. Elamipretide protects mitochondria from oxidative damage by stabilising cardiolipin.
Technical Context
Major ROS: superoxide anion (O2•⁻ — produced by mitochondrial complexes I and III, and by NOX enzymes), hydrogen peroxide (H2O2 — produced from superoxide by SOD, also a signalling molecule at low concentrations), hydroxyl radical (•OH — produced from H2O2 by Fenton reaction with Fe²⁺/Cu⁺, extremely reactive, no enzymatic defence), and peroxynitrite (ONOO⁻ — produced from superoxide + nitric oxide, damaging to proteins and DNA). ROS in physiology: immune defence (neutrophil/macrophage respiratory burst killing pathogens), cell signalling (H2O2 as a second messenger in growth factor signalling), and gene regulation (NF-κB and Nrf2 pathways are redox-sensitive). ROS in pathology: when production exceeds antioxidant capacity → oxidative damage to lipids, proteins, and DNA → contributes to ageing, neurodegeneration, cardiovascular disease, cancer, and diabetes. For peptide drugs, ROS are relevant to: formulation stability (oxidation is a primary peptide degradation pathway — Met, Trp, Cys residues are susceptible) and therapeutic mechanism (elamipretide's mitochondrial ROS reduction).