PRKN regulates inner mitochondrial membrane PHB2 during mitophagy
PINK1 (PTEN induced kinase 1) and PRKN-mediated mitophagy is an important mitochondrial quality control pathway which selectively degrades damaged mitochondria and is tightly associated with neurodegenerative diseases, including Parkinson disease and amyotrophic lateral sclerosis. The current model...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/27694127.2022.2164643 |
| _version_ | 1797685740184797184 |
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| author | Shan Sun Hongfeng Wang Qilian Ma Ningning Li Mian Cao Kin Yip Tam Zheng Ying |
| author_facet | Shan Sun Hongfeng Wang Qilian Ma Ningning Li Mian Cao Kin Yip Tam Zheng Ying |
| author_sort | Shan Sun |
| collection | DOAJ |
| description | PINK1 (PTEN induced kinase 1) and PRKN-mediated mitophagy is an important mitochondrial quality control pathway which selectively degrades damaged mitochondria and is tightly associated with neurodegenerative diseases, including Parkinson disease and amyotrophic lateral sclerosis. The current model of PINK1-PRKN-mediated mitophagy is that PRKN ubiquitinates multiple outer mitochondrial membrane (OMM) proteins, and then the ubiquitin chains on the OMM interact with autophagy receptors which bind Atg8-family protein labeled phagophores. However, little work has been focused on the PRKN-mediated ubiquitination of inner mitochondrial membrane (IMM) proteins during mitophagy. Our recent work revealed that PRKN binds and ubiquitinates PHB2 (prohibitin 2), an essential IMM protein which was previously recognized as a mitophagy receptor, after the OMM is ruptured by proteasomal degradation. Using biochemical and microscopy approaches, we found that mutations of PRKN-targeted ubiquitination sites on PHB2 decrease the recognition of damaged mitochondria by the phagophore and the clearance of damaged mitochondria. In conclusion, our findings revealed a critical role for PRKN-PHB2 interaction in mitochondrial quality control by regulating IMM-associated recognition of mitochondria by the autophagy machinery. |
| first_indexed | 2024-03-12T00:55:42Z |
| format | Article |
| id | doaj.art-eaa32c2b227f44b3b48853e7abf3ed15 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-12T00:55:42Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-eaa32c2b227f44b3b48853e7abf3ed152023-09-14T13:24:40ZengTaylor & Francis GroupAutophagy Reports2769-41272023-12-012110.1080/27694127.2022.21646432164643PRKN regulates inner mitochondrial membrane PHB2 during mitophagyShan Sun0Hongfeng Wang1Qilian Ma2Ningning Li3Mian Cao4Kin Yip Tam5Zheng Ying6Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow UniversityJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow UniversityJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow UniversityJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow UniversityProgramme in Neuroscience and Behavioural Disorders, Duke-NUS Medical SchoolUniversity of MacauJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow UniversityPINK1 (PTEN induced kinase 1) and PRKN-mediated mitophagy is an important mitochondrial quality control pathway which selectively degrades damaged mitochondria and is tightly associated with neurodegenerative diseases, including Parkinson disease and amyotrophic lateral sclerosis. The current model of PINK1-PRKN-mediated mitophagy is that PRKN ubiquitinates multiple outer mitochondrial membrane (OMM) proteins, and then the ubiquitin chains on the OMM interact with autophagy receptors which bind Atg8-family protein labeled phagophores. However, little work has been focused on the PRKN-mediated ubiquitination of inner mitochondrial membrane (IMM) proteins during mitophagy. Our recent work revealed that PRKN binds and ubiquitinates PHB2 (prohibitin 2), an essential IMM protein which was previously recognized as a mitophagy receptor, after the OMM is ruptured by proteasomal degradation. Using biochemical and microscopy approaches, we found that mutations of PRKN-targeted ubiquitination sites on PHB2 decrease the recognition of damaged mitochondria by the phagophore and the clearance of damaged mitochondria. In conclusion, our findings revealed a critical role for PRKN-PHB2 interaction in mitochondrial quality control by regulating IMM-associated recognition of mitochondria by the autophagy machinery.http://dx.doi.org/10.1080/27694127.2022.2164643map1lc3b/lc3bmitophagyphb2prknubiquitination |
| spellingShingle | Shan Sun Hongfeng Wang Qilian Ma Ningning Li Mian Cao Kin Yip Tam Zheng Ying PRKN regulates inner mitochondrial membrane PHB2 during mitophagy Autophagy Reports map1lc3b/lc3b mitophagy phb2 prkn ubiquitination |
| title | PRKN regulates inner mitochondrial membrane PHB2 during mitophagy |
| title_full | PRKN regulates inner mitochondrial membrane PHB2 during mitophagy |
| title_fullStr | PRKN regulates inner mitochondrial membrane PHB2 during mitophagy |
| title_full_unstemmed | PRKN regulates inner mitochondrial membrane PHB2 during mitophagy |
| title_short | PRKN regulates inner mitochondrial membrane PHB2 during mitophagy |
| title_sort | prkn regulates inner mitochondrial membrane phb2 during mitophagy |
| topic | map1lc3b/lc3b mitophagy phb2 prkn ubiquitination |
| url | http://dx.doi.org/10.1080/27694127.2022.2164643 |
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