A new study entitled “Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD” published in the Journal of Clinical Investigation shows how cigarette smoke leads to cell death, a key process in the development of chronic obstructive pulmonary disease. The findings put into better focus the already established correlation between smoking and diseases of the lung.

Chronic obstructive pulmonary disease (COPD) is characterized by chronically poor airflow, and is frequently associated with emphysema (loss of alveolar surface area) and bronchitis (a condition where occurs inflammation of the mucous membranes of the bronchi). Disease severity escalates with time and was ranked as the fourth leading cause of mortality worldwide. In 2011, 13 million American adults were estimated to suffer from COPD, according to The American Lung Association. The major risk factor for COPD is cigarette smoke. However, the exact underlying trigger for the disease remains incompletely understood.

Now, the team of researchers from Sanford I. Weill Chairman of the Weill Department of Medicine, led by Dr. Augustine M.K. Choi, discovered how cigarette smoke triggers cell death. Previously, the researchers showed that a regulatory pathway responsible for the degradation of dysfunctional cellular components — autophagy — was exacerbated in lung tissue derived from COPD patients and mice chronically exposed to CS, leading to lung epithelial cell death, airway dysfunction, and emphysema.

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In this study, the researchers used cultured pulmonary epithelial cells and mouse models to identify a new cellular pathway — mitophagy — that targets mitochondria for autophagic degradation. Mitophagy promotes the homeostatic control of the cells by maintaining a healthy mitochondrial population. The authors found that cigarette smoke causes mitochondria to stop working properly, leading to the trigger of mitophagy. They further demonstrated that mitophagy was associated with necroptosis (a programmed form of necrotic cell death) of epithelial cells, in response to cigarette smoke exposure.

The authors identified a mitophagy-dependent necroptosis pathway with clear implications to COPD pathogenesis, therefore suggesting this unknown pathway as a potential new therapeutic target to treat COPD.