Fig. 1

Proposed model for mitochondria-centered pathogenesis in ROS-induced lung diseases. Reactive oxygen species (ROS), commonly from exogenous exposure to smoke and air pollution, can be inhaled by the lungs. The superoxide anion radical (O ^·−₂ ) can react with NO to form the highly reactive peroxynitrite molecule (ONOO⁻). In the presence of chloride (Cl⁻) and bromide (Br⁻) ions, the very damaging oxidants hypochlorous acid (HOCl) and hypobromous acid (HOBr) are generated from hydrogen peroxidase (H₂O₂). (1) ROS-induced mitochondrial dysfunction: when the concentration of ROS increases in mitochondria, the electron chain transfer (ETC) complex becomes defective and leads to mitochondrial membrane potential loss and membrane permeability increases. (2) Mitochondrial DNA (mtDNA)-associated immune response: damaged mtDNA fragments are released from mitochondria. The immunogenic particles can recruit various immune cells, such as macrophages, TLR9⁺-T cells and neutrophils, to the damaged area to initiate inflammatory and immunological reactions