PINK1 regulated mitophagy is evident in skeletal muscles
ABSTRACTPINK1, mutated in familial forms of Parkinson’s disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this p...
| Main Authors: | , , , , , , |
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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 |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2024.2326402 |
| _version_ | 1797265457966743552 |
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| author | Francois Singh Lea Wilhelm Alan R. Prescott Kevin Ostacolo Jin-Feng Zhao Margret H. Ogmundsdottir Ian G. Ganley |
| author_facet | Francois Singh Lea Wilhelm Alan R. Prescott Kevin Ostacolo Jin-Feng Zhao Margret H. Ogmundsdottir Ian G. Ganley |
| author_sort | Francois Singh |
| collection | DOAJ |
| description | ABSTRACTPINK1, mutated in familial forms of Parkinson’s disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this pathway in vivo, we used mito-QC mice in which loss of PINK1 was combined with the mitochondrial-associated POLGD257A mutation. We focused on skeletal muscle as gene expression data indicates that this tissue has the highest PINK1 levels. We found that loss of PINK1 in oxidative hindlimb muscle significantly reduced mitophagy. Of interest, the presence of the POLGD257A mutation, while having a minor effect in most tissues, restored levels of muscle mitophagy caused by the loss of PINK1. Although our observations highlight that multiple mitophagy pathways operate within a single tissue, we identify skeletal muscle as a tissue of choice for the study of PINK1-dependant mitophagy under basal conditions. |
| first_indexed | 2024-04-25T00:45:07Z |
| format | Article |
| id | doaj.art-5b57ed0a9adb48e88193d7ed8114fd86 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-04-25T00:45:07Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-5b57ed0a9adb48e88193d7ed8114fd862024-03-12T06:15:33ZengTaylor & Francis GroupAutophagy Reports2769-41272024-12-013110.1080/27694127.2024.2326402PINK1 regulated mitophagy is evident in skeletal musclesFrancois Singh0Lea Wilhelm1Alan R. Prescott2Kevin Ostacolo3Jin-Feng Zhao4Margret H. Ogmundsdottir5Ian G. Ganley6MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UKMRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UKDundee Imaging Facility,School of Life Sciences, University of Dundee, Dundee, UKDepartment of Anatomy, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, IcelandMRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UKDepartment of Anatomy, Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, IcelandMRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UKABSTRACTPINK1, mutated in familial forms of Parkinson’s disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this pathway in vivo, we used mito-QC mice in which loss of PINK1 was combined with the mitochondrial-associated POLGD257A mutation. We focused on skeletal muscle as gene expression data indicates that this tissue has the highest PINK1 levels. We found that loss of PINK1 in oxidative hindlimb muscle significantly reduced mitophagy. Of interest, the presence of the POLGD257A mutation, while having a minor effect in most tissues, restored levels of muscle mitophagy caused by the loss of PINK1. Although our observations highlight that multiple mitophagy pathways operate within a single tissue, we identify skeletal muscle as a tissue of choice for the study of PINK1-dependant mitophagy under basal conditions.https://www.tandfonline.com/doi/10.1080/27694127.2024.2326402Parkinson’sPINK1mitophagymutatorPOLGmuscle |
| spellingShingle | Francois Singh Lea Wilhelm Alan R. Prescott Kevin Ostacolo Jin-Feng Zhao Margret H. Ogmundsdottir Ian G. Ganley PINK1 regulated mitophagy is evident in skeletal muscles Autophagy Reports Parkinson’s PINK1 mitophagy mutator POLG muscle |
| title | PINK1 regulated mitophagy is evident in skeletal muscles |
| title_full | PINK1 regulated mitophagy is evident in skeletal muscles |
| title_fullStr | PINK1 regulated mitophagy is evident in skeletal muscles |
| title_full_unstemmed | PINK1 regulated mitophagy is evident in skeletal muscles |
| title_short | PINK1 regulated mitophagy is evident in skeletal muscles |
| title_sort | pink1 regulated mitophagy is evident in skeletal muscles |
| topic | Parkinson’s PINK1 mitophagy mutator POLG muscle |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2024.2326402 |
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