Positioned at the hub of cellular metabolic flux, mitochondria are uniquely adapted to communicate with the nucleus to bring about cellular as well as extra-cellular responses to perceived threats. Lung epithelial cells are exposed to high levels of environmental stress and mitochondrial dysfunction critically contributes to the pathogenesis of a variety of lung diseases ranging from development of smoking related COPD to hypoxia induced pulmonary arterial hypertension (PAH). Mitochondria targeted antioxidants substantially improve abnormal cellular biology of airway smooth muscle from COPD patients. This session will review the current knowledge on the role of mitochondrial dysfunction in connecting environmental stress to lung disease, recent advances in targeting mitochondria and the therapeutic potential for such strategies.