Alterations of PINK1-PRKN signaling in mice during normal aging
The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the signifi...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Autophagy Reports |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2024.2434379 |
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| author | Zahra Baninameh Jens O. Watzlawik Xu Hou Tyrique Richardson Nicholas W. Kurchaba Tingxiang Yan Damian N. Di Florio DeLisa Fairweather Lu Kang Justin H. Nguyen Takahisa Kanekiyo Dennis W. Dickson Sachiko Noda Shigeto Sato Nobutaka Hattori Matthew S. Goldberg Ian G. Ganley Kelly L. Stauch Fabienne C. Fiesel Wolfdieter Springer |
| author_facet | Zahra Baninameh Jens O. Watzlawik Xu Hou Tyrique Richardson Nicholas W. Kurchaba Tingxiang Yan Damian N. Di Florio DeLisa Fairweather Lu Kang Justin H. Nguyen Takahisa Kanekiyo Dennis W. Dickson Sachiko Noda Shigeto Sato Nobutaka Hattori Matthew S. Goldberg Ian G. Ganley Kelly L. Stauch Fabienne C. Fiesel Wolfdieter Springer |
| author_sort | Zahra Baninameh |
| collection | DOAJ |
| description | The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.Abbreviations: ECL: electrochemiluminescence; ELISA: enzyme-linked immunosorbent assay; MSD: Meso Scale Discovery; PD: Parkinson disease; p-S65-Ub: Serine-65 phosphorylated ubiquitin; RT-PCR: real-time polymerase chain reaction; Ub: ubiquitin; WT: wild-type. |
| format | Article |
| id | doaj-art-865f7af7609a45dfb4dd9f54b9f42a6a |
| institution | Kabale University |
| issn | 2769-4127 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-865f7af7609a45dfb4dd9f54b9f42a6a2024-12-09T07:19:32ZengTaylor & Francis GroupAutophagy Reports2769-41272024-12-013110.1080/27694127.2024.2434379Alterations of PINK1-PRKN signaling in mice during normal agingZahra Baninameh0Jens O. Watzlawik1Xu Hou2Tyrique Richardson3Nicholas W. Kurchaba4Tingxiang Yan5Damian N. Di Florio6DeLisa Fairweather7Lu Kang8Justin H. Nguyen9Takahisa Kanekiyo10Dennis W. Dickson11Sachiko Noda12Shigeto Sato13Nobutaka Hattori14Matthew S. Goldberg15Ian G. Ganley16Kelly L. Stauch17Fabienne C. Fiesel18Wolfdieter Springer19Department of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Cardiovascular Medicine, Mayo Clinic,Jacksonville, FL, USADivision of Transplant Surgery, Department of Transplantation, Mayo Clinic,Jacksonville, FL, USADivision of Transplant Surgery, Department of Transplantation, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neurology, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Neurology, Juntendo University Graduate School of Medicine, Tokyo, JapanDepartment of Neurology, Juntendo University Graduate School of Medicine, Tokyo, JapanCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USAMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UKDepartment of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USADepartment of Neuroscience, Mayo Clinic,Jacksonville, FL, USAThe ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.Abbreviations: ECL: electrochemiluminescence; ELISA: enzyme-linked immunosorbent assay; MSD: Meso Scale Discovery; PD: Parkinson disease; p-S65-Ub: Serine-65 phosphorylated ubiquitin; RT-PCR: real-time polymerase chain reaction; Ub: ubiquitin; WT: wild-type.https://www.tandfonline.com/doi/10.1080/27694127.2024.2434379agingbrainheartmicemitochondriamitophagy |
| spellingShingle | Zahra Baninameh Jens O. Watzlawik Xu Hou Tyrique Richardson Nicholas W. Kurchaba Tingxiang Yan Damian N. Di Florio DeLisa Fairweather Lu Kang Justin H. Nguyen Takahisa Kanekiyo Dennis W. Dickson Sachiko Noda Shigeto Sato Nobutaka Hattori Matthew S. Goldberg Ian G. Ganley Kelly L. Stauch Fabienne C. Fiesel Wolfdieter Springer Alterations of PINK1-PRKN signaling in mice during normal aging Autophagy Reports aging brain heart mice mitochondria mitophagy |
| title | Alterations of PINK1-PRKN signaling in mice during normal aging |
| title_full | Alterations of PINK1-PRKN signaling in mice during normal aging |
| title_fullStr | Alterations of PINK1-PRKN signaling in mice during normal aging |
| title_full_unstemmed | Alterations of PINK1-PRKN signaling in mice during normal aging |
| title_short | Alterations of PINK1-PRKN signaling in mice during normal aging |
| title_sort | alterations of pink1 prkn signaling in mice during normal aging |
| topic | aging brain heart mice mitochondria mitophagy |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2024.2434379 |
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