Mitochondrion: A Missing Link in Asthma Pathogenesis

Abstract

Asthma is a multifactorial airway disease with airway hyperresponsiveness, airway inflammation, goblet cell metaplasia, and structural changes including airway smooth muscle proliferation and subepithelial fibrosis. Airway epithelial injury and apoptosis is an important triggering and amplification point in asthma pathogenesis, and mitochondrial dysfunction in epithelial cells appears to play an important role. On the other hand, mitochondrial biogenesis is an important aspect of smooth muscle hypertrophy and fibroblast proliferation, which leads to airway remodeling and hyperresponsiveness. In mice, preexisting mitochondrial dysfunction has been shown to potentiate allergic experimental asthma. In this review, we summarize the current understanding on the involvement of mitochondria in asthma pathogenesis, discuss the probable points of intersection between lung pathobiology and mitochondrial biology, and speculate regarding the road ahead. Mitochondrial influence on cellular oxidative and nitrative stress, apoptosis, and calcium homeostasis is covered in detail, as well as the role of molecules like nitric oxide synthase, asymmetric dimethyl arginine (ADMA), and peroxynitrite on mitochondrial function, epithelial injury, and asthma. Potential therapeutic strategies involving coenzyme Q, vitamin E, and esculetin that influence mitochondrial function and alleviate features of asthma are also discussed.