DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen

• Published in: International journal of molecular sciences Vol. 22; no. 20; p. 11125
• Main Authors: Bruno, Sierra R, Kumar, Amit, Mark, Zoe F, Chandrasekaran, Ravishankar, Nakada, Emily, Chamberlain, Nicolas, Mihavics, Bethany, Walzer, Joseph, Cahoon, Jonathon, Dixon, Anne E, Cunniff, Brian, Anathy, Vikas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-10-2021; MDPI
• Subjects: Ablation; Allergens; Allergens - pharmacology; allergic airway disease; Allergies; Animals; Apoptosis; Asthma; Bronchi - drug effects; Bronchi - physiology; Cell death; Cells, Cultured; Chemokines; Cytokines; Disease; DRP1; Dynamin; Dynamins - genetics; Dynamins - physiology; epithelial cell; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; Fusion protein; Gene expression; HDM; Humans; Inflammation; Inflammatory response; Lung - drug effects; Lung - metabolism; Lung - pathology; Lungs; Mice; Mice, Transgenic; Mitochondria; Mitochondrial Dynamics - genetics; mitochondrial fission; Mucin; Phosphorylation; Proteins; Respiratory Hypersensitivity - chemically induced; Respiratory Hypersensitivity - genetics; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - metabolism; Respiratory Mucosa - drug effects; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Respiratory tract; Transcription; HDM; allergic airway disease; epithelial cell; mitochondrial fission; DRP1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222011125

Mitochondria regulate a myriad of cellular functions. Dysregulation of mitochondrial control within airway epithelial cells has been implicated in the pro-inflammatory response to allergens in asthma patients. Because of their multifaceted nature, mitochondrial structure must be tightly regulated through fission and fusion. Dynamin Related Protein 1 (DRP1) is a key driver of mitochondrial fission. During allergic asthma, airway epithelial mitochondria appear smaller and structurally altered. The role of DRP1-mediated mitochondrial fission, however, has not been fully elucidated in epithelial response to allergens. We used a Human Bronchial Epithelial Cell line (HBECs), primary Mouse Tracheal Epithelial Cells (MTECs), and conditional DRP1 ablation in lung epithelial cells to investigate the impact of mitochondrial fission on the pro-inflammatory response to house dust mite (HDM) in vitro and in vivo. Our data suggest that, following HDM challenge, mitochondrial fission is rapidly upregulated in airway epithelial cells and precedes production of pro-inflammatory cytokines and chemokines. Further, deletion of
in lung epithelial cells leads to decreased fission and enhanced pro-inflammatory signaling in response to HDM in vitro, as well as enhanced airway hyper-responsiveness (AHR), inflammation, differential mucin transcription, and epithelial cell death in vivo. Mitochondrial fission, therefore, regulates the lung epithelial pro-inflammatory response to HDM.