The pathophysiological role of mitochondrial oxidative stress in lung diseases

Our plain-English summary of The pathophysiological role of mitochondrial oxidative stress in lung diseases, by X. Liu, Z. Chen (Journal of Translational Medicine, 2017).

The study

• Authors: X. Liu, Z. Chen
• Journal: Journal of Translational Medicine
• Published: 2017;15(1):207
• Type of article: Review
• Cited by: 149 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This article was a review by two authors in Shanghai, China, not a new study. It described published research on how reactive oxygen species, harmful oxygen-based molecules, damage mitochondria (the energy-producing parts of cells) and mitochondrial DNA in lung diseases. These diseases included lung fibrosis, asbestosis, chronic obstructive pulmonary disease, asthma, acute lung injury and lung cancer. It also covered possible antioxidant treatments. On asbestos, the authors summarized earlier work reporting that asbestos fibers taken into lung lining cells led to iron-derived reactive oxygen species, mitochondrial DNA damage and cell death. They cited a study reporting raised mitochondrial Rac-1 levels in lung immune cells (alveolar macrophages) from patients with asbestosis. They also cited a mouse study in which catalase given into the windpipe of asbestos-treated mice prevented lung fibrosis. The article did not name specific asbestos fiber types and did not discuss mesothelioma. The authors concluded that new approaches to raise lung antioxidant levels would help treat lung diseases lacking effective treatment. They noted that many targets found in animal models still need to be investigated in humans.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published laboratory, animal and human studies; no new data were collected
• Who was studied: No patients or animals were studied by the authors; the review drew on previously published cell, animal and human studies
• Exposure: Reactive oxygen species from outside sources (gases, airborne particles, cigarette smoke, asbestos fibers) and from the body's own cells; asbestos fiber types were not specified
• Main results:
  • The review described earlier research reporting that asbestos fibers are taken into alveolar epithelial (lung lining) cells, leading to iron-derived reactive oxygen species, mitochondrial DNA damage and programmed cell death
  • The review cited a study (Carter and colleagues) reporting raised mitochondrial Rac-1 levels in alveolar macrophages from patients with asbestosis
  • The review cited a mouse study in which catalase given into the windpipe of asbestos-treated mice prevented pulmonary fibrosis
  • The review cited work in which increasing a mitochondrial DNA-repair enzyme (mt-OGG1) helped lung lining cells survive asbestos-induced mitochondrial oxidative stress
  • The review cited a study in which mice lacking vimentin had less asbestos-induced lung fibrosis
  • The authors stated that the reviewed data supported a key role for p53 in mitochondrial DNA damage in lung lining cells during fibrosis-promoting responses after asbestos exposure
• The authors' conclusion: The authors concluded that developing new pharmacological, dietary and genetic approaches to increase lung antioxidant levels would be helpful for treating lung diseases that currently have no effective treatment options
• Limitations the authors state:
  • Many targets identified in animal models still need to be investigated in humans
  • Results on dietary antioxidant vitamins were inconsistent, and robust clinical trials are needed

Topics

Medical terms in this study, explained in our Lexicon: Oxidative Stress, Reactive Oxygen Species (ROS), Fibrosis, Lung Cancer, Alveolar Macrophage, Superoxide.

Related studies

• Mitochondria-derived reactive intermediate species mediate asbestos-induced genotoxicity and oxidative stress-responsive signaling pathways — S.X. Huang, M.A. Partridge, et al. (2012)
• Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells — S.J. Kim, P. Cheresh, et al. (2014)
• Pifithrin-μ induces necroptosis through oxidative mitochondrial damage but accompanies epithelial-mesenchymal transition-like phenomenon in malignant mesothelioma cells under lactic acidosis — Y.J. Lee, K.S. Park, et al. (2019)
• Rapid and easy method for monitoring oxidative stress markers in body fluids of patients with asbestos or silica-induced lung diseases — K. Syslová, P. Kacer, et al. (2009)
• Oxidative stress markers in exhaled breath condensate in lung fibroses are not significantly affected by systemic diseases — D. Pelclová, Z. Fenclová, et al. (2011)
• Negative modulation of mitochondrial oxidative phosphorylation by epigallocatechin-3 gallate leads to growth arrest and apoptosis in human malignant pleural mesothelioma cells — D. Valenti, L. de Bari, et al. (2013)

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