Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy
Abstract Autophagy of damaged mitochondria, called mitophagy, is an important organelle quality control process involved in the pathogenesis of inflammation, cancer, aging, and age-associated diseases. Many of these disorders are associated with altered expression of the inner mitochondrial membrane...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26775-x |
| _version_ | 1828069544879456256 |
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| author | Kibrom M. Alula Yaritza Delgado-Deida Rosemary Callahan Andreas Till Lucia Underwood Winston E. Thompson Rhonda F. Souza Themistocles Dassopoulos Joseph Onyiah K. Venuprasad Arianne L. Theiss |
| author_facet | Kibrom M. Alula Yaritza Delgado-Deida Rosemary Callahan Andreas Till Lucia Underwood Winston E. Thompson Rhonda F. Souza Themistocles Dassopoulos Joseph Onyiah K. Venuprasad Arianne L. Theiss |
| author_sort | Kibrom M. Alula |
| collection | DOAJ |
| description | Abstract Autophagy of damaged mitochondria, called mitophagy, is an important organelle quality control process involved in the pathogenesis of inflammation, cancer, aging, and age-associated diseases. Many of these disorders are associated with altered expression of the inner mitochondrial membrane (IMM) protein Prohibitin 1. The mechanisms whereby dysfunction occurring internally at the IMM and matrix activate events at the outer mitochondrial membrane (OMM) to induce mitophagy are not fully elucidated. Using the gastrointestinal epithelium as a model system highly susceptible to autophagy inhibition, we reveal a specific role of Prohibitin-induced mitophagy in maintaining intestinal homeostasis. We demonstrate that Prohibitin 1 induces mitophagy in response to increased mitochondrial reactive oxygen species (ROS) through binding to mitophagy receptor Nix/Bnip3L and independently of Parkin. Prohibitin 1 is required for ROS-induced Nix localization to mitochondria and maintaining homeostasis of epithelial cells highly susceptible to mitochondrial dysfunction. |
| first_indexed | 2024-04-11T00:22:44Z |
| format | Article |
| id | doaj.art-409c2db6f86d4000bd758ce74a53ab92 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T00:22:44Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-409c2db6f86d4000bd758ce74a53ab922023-01-08T12:11:05ZengNature PortfolioScientific Reports2045-23222023-01-0113111610.1038/s41598-022-26775-xInner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagyKibrom M. Alula0Yaritza Delgado-Deida1Rosemary Callahan2Andreas Till3Lucia Underwood4Winston E. Thompson5Rhonda F. Souza6Themistocles Dassopoulos7Joseph Onyiah8K. Venuprasad9Arianne L. Theiss10Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of MedicineDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of MedicineDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of MedicineDepartment of Internal Medicine, University Hospital BonnDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of MedicineDepartment of Obstetrics and Gynecology, Morehouse School of MedicineCenter for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott & White Research InstituteCenter for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott & White Research InstituteDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of MedicineCollege of Medicine, University of Texas Southwestern Medical CenterDivision of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of MedicineAbstract Autophagy of damaged mitochondria, called mitophagy, is an important organelle quality control process involved in the pathogenesis of inflammation, cancer, aging, and age-associated diseases. Many of these disorders are associated with altered expression of the inner mitochondrial membrane (IMM) protein Prohibitin 1. The mechanisms whereby dysfunction occurring internally at the IMM and matrix activate events at the outer mitochondrial membrane (OMM) to induce mitophagy are not fully elucidated. Using the gastrointestinal epithelium as a model system highly susceptible to autophagy inhibition, we reveal a specific role of Prohibitin-induced mitophagy in maintaining intestinal homeostasis. We demonstrate that Prohibitin 1 induces mitophagy in response to increased mitochondrial reactive oxygen species (ROS) through binding to mitophagy receptor Nix/Bnip3L and independently of Parkin. Prohibitin 1 is required for ROS-induced Nix localization to mitochondria and maintaining homeostasis of epithelial cells highly susceptible to mitochondrial dysfunction.https://doi.org/10.1038/s41598-022-26775-x |
| spellingShingle | Kibrom M. Alula Yaritza Delgado-Deida Rosemary Callahan Andreas Till Lucia Underwood Winston E. Thompson Rhonda F. Souza Themistocles Dassopoulos Joseph Onyiah K. Venuprasad Arianne L. Theiss Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy Scientific Reports |
| title | Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy |
| title_full | Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy |
| title_fullStr | Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy |
| title_full_unstemmed | Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy |
| title_short | Inner mitochondrial membrane protein Prohibitin 1 mediates Nix-induced, Parkin-independent mitophagy |
| title_sort | inner mitochondrial membrane protein prohibitin 1 mediates nix induced parkin independent mitophagy |
| url | https://doi.org/10.1038/s41598-022-26775-x |
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