title: Mitochondria dysfunction: A novel therapeutic target in pathological lung remodeling or bystander?
abstract: The renascence in mitochondrial research has fueled breakthroughs in our understanding of mitochondrial biology identifying major roles in biological processes ranging from cellular oxygen sensing and regulation of intracellular calcium levels through to initiation of apoptosis or a shift in cell phenotype. Chronic respiratory diseases are no exception to the resurgent interest in mitochondrial biology. Microscopic observations of lungs from patients with chronic respiratory diseases such as pulmonary arterial hypertension, asthma and COPD show accumulation of dysmorphic mitochondria and provide the first evidence of mitochondrial dysfunction in diseased lungs. Recent mechanistic insights have established links between mitochondrial dysfunction or aberrant biogenesis and the pathogenesis of chronic respiratory diseases through playing a causative role in structural remodeling of the lung. The aim here is to discuss the case for a mitochondrial basis of lung remodeling in patients with chronic respiratory diseases. The present article will focus on the question of whether currently available data supports mitochondrial mechanisms as a viable point of therapeutic intervention in respiratory diseases and suggestions for future avenues of research in this rapidly evolving field.
authors.affiliation: Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: david.rowlands@novartis.com.
authors.forename: David J
authors.initials: DJ
authors.lastname: Rowlands
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002908:Chronic Disease; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008171:Lung Diseases / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D017382:Reactive Oxygen Species
keywords: Lung; Mitochondria; Mitophagy; ROS; Remodeling; Therapy