TABLE 1

Potential mitochondrial targeting treatments for lung diseases

DiseaseCell targetTherapeutic compoundsMitochondrial targetModelMain finding
Asthma
Smooth muscle cellGallopamilMitochondrial biogenesisHumanDecrease of SMC mass and exacerbation rate
MacrophageEtomoxirFatty acid oxidation pathwayMouseDecreased TH2 inflammation
FibroblastAzithromycinSenescenceHumanImproved peak expiratory flow, symptoms and quality of life
NAMetforminROS productionHumanDecreased severe exacerbations
NARoxithromycinSenescenceRatDecreased airway remodelling
NARapamycinSenescenceMouseDecreased eosinophilic airway inflammation
NAResveratrolSenescenceMouseDecreased fibrotic responses and airway inflammation
NAL-arginineNO pathwayMouseDecreased AHR and inflammation
PAH
NAMetforminSenescenceRatIncreased endothelial function and decrease arterial remodelling
NARapamycinSenescenceRatDecreased pulmonary artery smooth muscle cell proliferation
NAMitoQROS productionMouseDecreased right ventricular hypertrophy
Acute lung injury
NANAAdaptive mitochondrial biogenesis and mitophagy stimulationMouseRemoves damaged mitochondria and increases tissue repair and cell survival
Alveolar epithelial cellBone marrow–derived mesenchymal stem cells mitochondria transferNAMouseRestoration of alveolar bioenergetics and protection against LPS-induced ALI
NAFusion protein targeting the DNA repair enzyme 8-oxoguanine-DNA glycosylase 1 to the mitochondriaMitochondrial ROSMouseEnhanced survival under ventilator-induced lung injury
Epithelial cellMildronateCarnitine synthesisMouseImproves lung function
NAMitoTEMPOMitochondrial ROSInfluenza A virus infected mouseReduction in lung inflammation, neutrophil infiltration, viral titre and mortality
Epithelial cellMitoQMitochondrial ROSHuman Epithelial cells and mouseReduced epithelial RSV production and inflammation
Epithelial cellTargeting dynein motor proteinMitochondrial ROSHuman Epithelial cellsReduced epithelial RSV production and inflammation
IPF
Alveolar epithelial cellThyroid hormone mimetics SobetiromeMitochondria biogenesisMouseDecreased bleomycin-induced pulmonary fibrosis
Alveolar epithelial cellGenetic over expression of mitochondrial-targeted catalaseMitochondrial ROSMouseDecreased asbestos or bleomycin-induced pulmonary fibrosis
FibroblastCarbon monoxideHeme oxygenaseMouseDecreased bleomycin-induced pulmonary fibrosis
Alveolar epithelial cellRapamycinMitochondrial biogenesisEpithelial cellsReduces mitochondrial biogenesis and cellular senescence in cultured alveolar epithelial cells
MyofibroblastPirfenidonePARK2-mediated mitophagyMouse and cellsInhibits lung fibrosis development in the setting of insufficient mitophagy
COPD
MacrophageCarbon monoxideHeme oxygenaseHumanReduced sputum eosinophilia and improved methacholine responsiveness
NASkQ1Mitochondrial ROSRatsPrevent and partially reverse age-related decline
Ciliated epithelial cellMdivi-1, a pharmacological inhibitor of Drp1MitophagyMiceRestores mucociliary dysfunction
Epithelial cellMitoTEMPOMitochondrial ROSHuman epithelial cellsInhibition of cigarette smoke extract induce mitochondria fragmentation
Smooth muscle cellMitoQMitochondrial ROSHuman smooth muscle cellsDecrease TGF-β induce ASM cell proliferation and CXCL8 release in HSMC
Smooth muscle cellMitoQMitochondrial ROSMouseReduced inflammation and airway hyperresponsiveness in ozone treated mouse
Endothelial cellMitochondria-targeted H2S donors AP39, AP123 and RT01Mitochondria proteins persulfidationHuman endothelial cellsDecrease cellular senescence
Mononuclear blood cellRapamycinmTOR pathwayHuman peripheral blood mononuclear cellsRestoring corticosteroid sensitivity
NADeferiproneMitochondrial iron redistributionMouseRestoring mucociliary function, inhibiting BAL infiltrates
NAResveratrolMitochondrial ROSMouseDelayed the loss of lung compliance, maintained lung structure and blocked parenchymal cell DNA damage
Lung cancer
Epithelial cellMitochondria-targeted mito-lonidamineOxidative phosphorylationHuman epithelial cell lineImproved 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.