DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen
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 th...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/20/11125 |
| _version_ | 1797514373395120128 |
|---|---|
| author | Sierra R. Bruno Amit Kumar Zoe F. Mark Ravishankar Chandrasekaran Emily Nakada Nicolas Chamberlain Bethany Mihavics Joseph Walzer Jonathon Cahoon Anne E. Dixon Brian Cunniff Vikas Anathy |
| author_facet | Sierra R. Bruno Amit Kumar Zoe F. Mark Ravishankar Chandrasekaran Emily Nakada Nicolas Chamberlain Bethany Mihavics Joseph Walzer Jonathon Cahoon Anne E. Dixon Brian Cunniff Vikas Anathy |
| author_sort | Sierra R. Bruno |
| collection | DOAJ |
| description | 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 <i>Drp1</i> 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. |
| first_indexed | 2024-03-10T06:30:42Z |
| format | Article |
| id | doaj.art-54d419f2f7554b4880466adf1325fd43 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:30:42Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-54d419f2f7554b4880466adf1325fd432023-11-22T18:34:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122201112510.3390/ijms222011125DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to AllergenSierra R. Bruno0Amit Kumar1Zoe F. Mark2Ravishankar Chandrasekaran3Emily Nakada4Nicolas Chamberlain5Bethany Mihavics6Joseph Walzer7Jonathon Cahoon8Anne E. Dixon9Brian Cunniff10Vikas Anathy11Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USADepartment of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USAMitochondria 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 <i>Drp1</i> 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.https://www.mdpi.com/1422-0067/22/20/11125mitochondrial fissionepithelial cellHDMallergic airway diseaseDRP1 |
| spellingShingle | Sierra R. Bruno Amit Kumar Zoe F. Mark Ravishankar Chandrasekaran Emily Nakada Nicolas Chamberlain Bethany Mihavics Joseph Walzer Jonathon Cahoon Anne E. Dixon Brian Cunniff Vikas Anathy DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen International Journal of Molecular Sciences mitochondrial fission epithelial cell HDM allergic airway disease DRP1 |
| title | DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen |
| title_full | DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen |
| title_fullStr | DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen |
| title_full_unstemmed | DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen |
| title_short | DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen |
| title_sort | drp1 mediated mitochondrial fission regulates lung epithelial response to allergen |
| topic | mitochondrial fission epithelial cell HDM allergic airway disease DRP1 |
| url | https://www.mdpi.com/1422-0067/22/20/11125 |
| work_keys_str_mv | AT sierrarbruno drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT amitkumar drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT zoefmark drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT ravishankarchandrasekaran drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT emilynakada drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT nicolaschamberlain drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT bethanymihavics drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT josephwalzer drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT jonathoncahoon drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT anneedixon drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT briancunniff drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen AT vikasanathy drp1mediatedmitochondrialfissionregulateslungepithelialresponsetoallergen |