Tuberc Respir Dis.  2016 Oct;79(4):207-213. 10.4046/trd.2016.79.4.207.

A Mitochondrial Perspective of Chronic Obstructive Pulmonary Disease Pathogenesis

• Kang MJ
• Shadel GS

• KMID: 2365312
• DOI: http://doi.org/10.4046/trd.2016.79.4.207

Abstract

Chronic obstructive pulmonary disease (COPD) encompasses several clinical syndromes, most notably emphysema and chronic bronchitis. Most of the current treatments fail to attenuate severity and progression of the disease, thereby requiring better mechanistic understandings of pathogenesis to develop disease-modifying therapeutics. A number of theories on COPD pathogenesis have been promulgated wherein an increase in protease burden from chronic inflammation, exaggerated production of reactive oxygen species and the resulting oxidant injury, or superfluous cell death responses caused by enhanced cellular injury/damage were proposed as the culprit. These hypotheses are not mutually exclusive and together likely represent the multifaceted biological processes involved in COPD pathogenesis. Recent studies demonstrate that mitochondria are involved in innate immune signaling that plays important roles in cigarette smoke-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. These responses are reviewed herein and synthesized into a view of COPD pathogenesis whereby mitochondria play a central role.

Keyword

Pulmonary Disease, Chronic Obstructive; Mitochondria; NLRX1 Protein, Human

MeSH Terms

Biological Processes
Bronchitis, Chronic
Cell Death
Emphysema
Inflammasomes
Inflammation
Mitochondria
Pneumonia
Pulmonary Disease, Chronic Obstructive*
Reactive Oxygen Species
Tobacco Products
Inflammasomes
Reactive Oxygen Species

Figure

• 

  Figure 1 Mitochondrial perspective of chronic obstructive pulmonary disease (COPD) pathogenesis. Nucleotide binding domain and leucine-rich-repeat-containing protein X1 (NLRX1), which might have a crucial inhibitory role to keep alveolar macrophages (AMs) in a quiescent homeostatic status, is suppressed in patients with COPD. The suppression of NLRX1 in AMs is associated with mitochondrial dysfunction and leads to the increase of inflammasome activation, protease burden as well as production of mitochondrial reactive oxygen species (ROS), which culminate in the development of COPD. CS: cigarette smoke; IL-18: interleukin 18; MMP: matrix metalloproteinase. Please see the main text for the explanation in detail. Modified from Yoon CM, et al. J Innate Immun 2016;8:121-835, with permission of S. Karger AG, Basel.

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