- Title
- Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?
- Creator
- Ng Kee Kwong, Francois; Nicholson, Andrew G.; Harrison, Celeste L.; Hansbro, Philip M.; Adcock, Ian M.; Chung, Kian Fan
- Relation
- European Respiratory Review Vol. 26, Issue 146, no. 170040
- Publisher Link
- http://dx.doi.org/10.1183/16000617.0040-2017
- Publisher
- European Respiratory Society
- Resource Type
- journal article
- Date
- 2017
- Description
- Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis. The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.
- Subject
- chronic obstructive pulmonary disease (COPD); nonsmall cell lung carcinoma; mitochondria; mitochondrial damage; oxidative stress; chronic inflammation
- Identifier
- http://hdl.handle.net/1959.13/1394827
- Identifier
- uon:33773
- Identifier
- ISSN:0905-9180
- Rights
- © ERS 2017. ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
- Language
- eng
- Full Text
- Reviewed
- Hits: 4800
- Visitors: 5110
- Downloads: 341
Collections
Goal 3: Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 339 KB | Adobe Acrobat PDF | View Details Download |