The pathophysiological role of mitochondrial oxidative stress in lung diseases - PubMed (original) (raw)

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The pathophysiological role of mitochondrial oxidative stress in lung diseases

Xiaojing Liu et al. J Transl Med. 2017.

Abstract

Mitochondria are critically involved in reactive oxygen species (ROS)-dependent lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial dysfunction, including electron transport chain impairment and mitochondrial membrane potential loss. Furthermore, damaged mtDNA also acts as a damage-associated molecular pattern (DAMP) that drives inflammatory and immune responses. In this review, crosstalk among alveolar epithelial cells, alveolar macrophages and mitochondria is examined. ROS-related transcription factors and downstream cell signaling pathways are also discussed. We conclude that targeting oxidative stress with antioxidant agents, such as thiol molecules, polyphenols and superoxide dismutase (SOD), and promoting mitochondrial biogenesis should be considered as novel strategies for treating lung diseases that currently have no effective treatment options.

Keywords: Antioxidant agents; Mitochondrial DNA; Reactive oxygen species.

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Figures

Fig. 1

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 (O2·−) 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

Fig. 2

Fig. 2

Mitochondrial dysfunction and diverse lung diseases. Mitochondrial dysfunction and mitochondrial DNA mutations and deletions can cause defects in energy metabolism and impair non-energetic pathways. Mitochondrial dysfunction is also associated with lung alveolar epithelial cell and alveolar macrophage apoptosis, which hinders lung repair and influences the expression of various reactive oxygen species-related genes. Thus, mitochondrial dysfunction can induce diverse degenerative lung diseases

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