title: Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.
abstract: Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases.
authors.affiliation: CSIR Institute of Genomics and Integrative Biology, Delhi, India a.agrawal@igib.in.
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: CSIR Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Ulaganathan
authors.initials: U
authors.lastname: Mabalirajan
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019069:Cell Respiration / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects / Q000276:immunology
keywords: asthma; chronic obstructive pulmonary disease; lung; mitochondria; pulmonary hypertension