TABLE 1.
Potential mitochondrial targeting treatments for lung diseases
| Disease | Cell target | Therapeutic compounds | Mitochondrial target | Model | Main finding |
| Asthma | |||||
| Smooth muscle cell | Gallopamil | Mitochondrial biogenesis | Human | Decrease of SMC mass and exacerbation rate | |
| Macrophage | Etomoxir | Fatty acid oxidation pathway | Mouse | Decreased TH2 inflammation | |
| Fibroblast | Azithromycin | Senescence | Human | Improved peak expiratory flow, symptoms and quality of life | |
| NA | Metformin | ROS production | Human | Decreased severe exacerbations | |
| NA | Roxithromycin | Senescence | Rat | Decreased airway remodelling | |
| NA | Rapamycin | Senescence | Mouse | Decreased eosinophilic airway inflammation | |
| NA | Resveratrol | Senescence | Mouse | Decreased fibrotic responses and airway inflammation | |
| NA | L-arginine | NO pathway | Mouse | Decreased AHR and inflammation | |
| PAH | |||||
| NA | Metformin | Senescence | Rat | Increased endothelial function and decrease arterial remodelling | |
| NA | Rapamycin | Senescence | Rat | Decreased pulmonary artery smooth muscle cell proliferation | |
| NA | MitoQ | ROS production | Mouse | Decreased right ventricular hypertrophy | |
| Acute lung injury | |||||
| NA | NA | Adaptive mitochondrial biogenesis and mitophagy stimulation | Mouse | Removes damaged mitochondria and increases tissue repair and cell survival | |
| Alveolar epithelial cell | Bone marrow–derived mesenchymal stem cells mitochondria transfer | NA | Mouse | Restoration of alveolar bioenergetics and protection against LPS-induced ALI | |
| NA | Fusion protein targeting the DNA repair enzyme 8-oxoguanine-DNA glycosylase 1 to the mitochondria | Mitochondrial ROS | Mouse | Enhanced survival under ventilator-induced lung injury | |
| Epithelial cell | Mildronate | Carnitine synthesis | Mouse | Improves lung function | |
| NA | MitoTEMPO | Mitochondrial ROS | Influenza A virus infected mouse | Reduction in lung inflammation, neutrophil infiltration, viral titre and mortality | |
| Epithelial cell | MitoQ | Mitochondrial ROS | Human Epithelial cells and mouse | Reduced epithelial RSV production and inflammation | |
| Epithelial cell | Targeting dynein motor protein | Mitochondrial ROS | Human Epithelial cells | Reduced epithelial RSV production and inflammation | |
| IPF | |||||
| Alveolar epithelial cell | Thyroid hormone mimetics Sobetirome | Mitochondria biogenesis | Mouse | Decreased bleomycin-induced pulmonary fibrosis | |
| Alveolar epithelial cell | Genetic over expression of mitochondrial-targeted catalase | Mitochondrial ROS | Mouse | Decreased asbestos or bleomycin-induced pulmonary fibrosis | |
| Fibroblast | Carbon monoxide | Heme oxygenase | Mouse | Decreased bleomycin-induced pulmonary fibrosis | |
| Alveolar epithelial cell | Rapamycin | Mitochondrial biogenesis | Epithelial cells | Reduces mitochondrial biogenesis and cellular senescence in cultured alveolar epithelial cells | |
| Myofibroblast | Pirfenidone | PARK2-mediated mitophagy | Mouse and cells | Inhibits lung fibrosis development in the setting of insufficient mitophagy | |
| COPD | |||||
| Macrophage | Carbon monoxide | Heme oxygenase | Human | Reduced sputum eosinophilia and improved methacholine responsiveness | |
| NA | SkQ1 | Mitochondrial ROS | Rats | Prevent and partially reverse age-related decline | |
| Ciliated epithelial cell | Mdivi-1, a pharmacological inhibitor of Drp1 | Mitophagy | Mice | Restores mucociliary dysfunction | |
| Epithelial cell | MitoTEMPO | Mitochondrial ROS | Human epithelial cells | Inhibition of cigarette smoke extract induce mitochondria fragmentation | |
| Smooth muscle cell | MitoQ | Mitochondrial ROS | Human smooth muscle cells | Decrease TGF-β induce ASM cell proliferation and CXCL8 release in HSMC | |
| Smooth muscle cell | MitoQ | Mitochondrial ROS | Mouse | Reduced inflammation and airway hyperresponsiveness in ozone treated mouse | |
| Endothelial cell | Mitochondria-targeted H2S donors AP39, AP123 and RT01 | Mitochondria proteins persulfidation | Human endothelial cells | Decrease cellular senescence | |
| Mononuclear blood cell | Rapamycin | mTOR pathway | Human peripheral blood mononuclear cells | Restoring corticosteroid sensitivity | |
| NA | Deferiprone | Mitochondrial iron redistribution | Mouse | Restoring mucociliary function, inhibiting BAL infiltrates | |
| NA | Resveratrol | Mitochondrial ROS | Mouse | Delayed the loss of lung compliance, maintained lung structure and blocked parenchymal cell DNA damage | |
| Lung cancer | |||||
| Epithelial cell | Mitochondria-targeted mito-lonidamine | Oxidative phosphorylation | Human epithelial cell line | Improved mitochondrial function and restores autophagy Metastasis reduction in experimental lung tumours |
PAH: pulmonary arterial hypertension; IPF: idiopathic pulmonary fibrosis; SMC: smooth muscle cell; TH: T-helper; NA: not addressed; ROS: reactive oxygen species; NO: nitric oxide; AHR: airway hyperreactivity; LPS: lipopolysaccharide; ALI: acute lung injury; RSV: respiratory syncytial virus; TGF: transforming growth factor; ASM: airway smooth muscle; HSMC: human smooth muscle cells; mTOR: mammalian target of rapamycin.