Targeting the mitochondria in chronic respiratory diseases

Chellappan, Dinesh Kumar; Paudel, Keshav Raj; Tan, Nian Wan; Cheong, Ka Seng; Khoo, Samantha Sert Qi; Seow, Su Min; Chellian, Jestin; Candasamy, Mayuren; Patel, Vyoma; Arora, Poonam; Singh, Pankaj Kumar; Singh, Sachin Kumar; Gupta, Gaurav; Oliver, Brian Gregory George; Hansbro, Philip M.; Dua, Kamal

doi:10.1016/j.mito.2022.09.003

Cited by 27 publications

(10 citation statements)

References 208 publications

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“…Bronchial epithelial cells play an essential role in asthma and mitochondrial dysfunction is implicated in asthmatic bronchial epithelial cells (AghapourRAPS et al, 2020). Drugs that improve mitochondrial dysfunction can be used for the treatment of asthma (Chellappan et al, 2022). However, the role of epithelial mitochondrial dysfunction in T2-low asthma remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Defects of the mitochondria play an essential role in the apoptosis of airway cells and lung fibrosis (Larson-Casey et al, 2020). Mitochondrial dysfunction has been associated with the pathogenesis of asthma (Chellappan et al, 2022). Airway epithelial cells play a pivotal role in the initiation and development of asthma (Coverstone et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria dysfunction in airway epithelial cells is associated with type 2-low asthma

Gao

Chen

et al. 2023

Front. Genet.

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Background: Type 2 (T2)-low asthma can be severe and corticosteroid-resistant. Airway epithelial cells play a pivotal role in the development of asthma, and mitochondria dysfunction is involved in the pathogenesis of asthma. However, the role of epithelial mitochondria dysfunction in T2-low asthma remains unknown.Methods: Differentially expressed genes (DEGs) were identified using gene expression omnibus (GEO) dataset GSE4302, which is originated from airway epithelial brushings from T2-high (n = 22) and T2-low asthma patients (n = 20). Gene set enrichment analysis (GSEA) was implemented to analyze the potential biological pathway involved between T2-low and T2-high asthma. T2-low asthma related genes were identified using weighted gene co-expression network analysis (WGCNA). The mitochondria-related genes (Mito-RGs) were referred to the Molecular Signatures Database (MSigDB). T2-low asthma related mitochondria (T2-low-Mito) DEGs were obtained by intersecting the DEGs, T2-low asthma related genes, and Mito-RGs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to further explore the potential function of the T2-low-Mito DEGs. In addition, the hub genes were further identified by protein-protein interaction (PPI), and the expressions of hub genes were verified in another GEO dataset GSE67472 and bronchial brushings from patients recruited at Tongji Hospital.Results: Six hundred and ninety-two DEGs, including 107 downregulated genes and 585 upregulated genes were identified in airway epithelial brushings from T2-high and T2-low asthma patients included in GSE4302 dataset. GSEA showed that mitochondrial ATP synthesis coupled electron transport is involved in T2-low asthma. Nine hundred and four T2-low asthma related genes were identified using WGCNA. Twenty-two T2-low-Mito DEGs were obtained by intersecting the DEGs, T2-low asthma and Mito-RGs. The GO enrichment analysis of the T2-low-Mito DEGs showed significant enrichment of mitochondrial respiratory chain complex assembly, and respiratory electron transport chain. PPI network was constructed using 22 T2-low-Mito DEGs, and five hub genes, ATP5G1, UQCR10, NDUFA3, TIMM10, and NDUFAB1, were identified. Moreover, the expression of these hub genes was validated in another GEO dataset, and our cohort of asthma patients.Conclusion: This study suggests that mitochondria dysfunction contributes to T2-low asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondria dysfunction in airway epithelial cells is associated with type 2-low asthma

Gao

Chen

et al. 2023

Front. Genet.

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“…However, stimulators of soluble guanylate cyclase (a target enzyme of NO in smooth muscle cells) in a rodent model exposed to cigarette smoke were beneficial for pulmonary vascular remodeling and prevented emphysema progression [ 117 ]. Another potential link between emphysema and endothelial dysfunction in COPD might be the aberrant purinergic signaling and elevated pulmonary ATP levels with plausible interactions with ongoing oxidative stress [ 118 , 119 , 120 ].…”

Section: Oxidative Stress—a Link Between Copd and Cardiovascular Como...mentioning

confidence: 99%

The Role of Oxidative Stress and Antioxidants in Cardiovascular Comorbidities in COPD

Miklós

Horváth

2023

Antioxidants

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Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in disease pathomechanisms. Unbalance between oxidants and antioxidant defense mechanisms amplifies the local inflammatory processes, worsens cardiovascular health, and contributes to COPD-related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures, with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced, with some suggestions for further research in the field.

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“…22 In addition, studies have confirmed that the occurrence and development of lung diseases partly contribute to the impairment of mitochondrial integrity and function. 23 Therefore, continuous exposure to various environmental pollutants, such as nanoparticles, can seriously damage mitochondria, disrupt cellular homeostasis, and ultimately change cell fate.…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, the morphology and structure of mitochondria are very flexible, whose dynamic modification can meet and participate in a variety of cellular processes, including autophagy . In addition, studies have confirmed that the occurrence and development of lung diseases partly contribute to the impairment of mitochondrial integrity and function . Therefore, continuous exposure to various environmental pollutants, such as nanoparticles, can seriously damage mitochondria, disrupt cellular homeostasis, and ultimately change cell fate.…”

Section: Introductionmentioning

confidence: 99%

Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

Yang,

Zhang,

et al. 2023

ACS Nano

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Targeting the mitochondria in chronic respiratory diseases

Cited by 27 publications

References 208 publications

Mitochondria dysfunction in airway epithelial cells is associated with type 2-low asthma

Mitochondria dysfunction in airway epithelial cells is associated with type 2-low asthma

The Role of Oxidative Stress and Antioxidants in Cardiovascular Comorbidities in COPD

Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

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