Mitochondria dysfunction: A novel therapeutic target in pathological lung remodeling or bystander?

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• 作者：David J. Rowlands ; ^{david.rowlands@novartis.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：18-FDG ; 18. [F]-fluoro-D-glucose ; AECII ; alveolar epithelial cell type II ; ATP ; adenosine triphosphate ; BMPR2 ; bone morphogenic protein receptor 2 ; CF ; cystic fibrosis ; CFTR ; cystic fibrosis transmembrane conductance regulator ; COPD ; chronic obstructive lung disease ; DAMPs ; damage-associated molecular pattern molecules ; DCA ; dichloroacetate ; DPLD ; diffuse parenchymal lung diseases ; Drp-1 ; dynamin related protein 1 ; ER ; endoplasmic reticulum ; FIS1 ; Mitochondrial fission 1 protein ; HIF-1α ; hypoxia
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：166
• 期：Complete
• 页码：96-105
• 全文大小：829 K

文摘

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.