Loss of Parkin impairs mitochondrial function and leads to muscle atrophy
Parkinson's disease is a neurodegenerative disease characterized by tremors, muscle stiffness, and muscle weakness. Molecular genetic analysis has confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated...
| Үндсэн зохиолчид: | , , , , |
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| Формат: | Journal Article |
| Хэл сонгох: | English |
| Хэвлэсэн: |
2020
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| Нөхцлүүд: | |
| Онлайн хандалт: | https://hdl.handle.net/10356/138111 |
| _version_ | 1826125831536115712 |
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| author | Peker, Nesibe Donipadi, Vinay Sharma, Mridula McFarlane, Craig Kambadur, Ravi |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Peker, Nesibe Donipadi, Vinay Sharma, Mridula McFarlane, Craig Kambadur, Ravi |
| author_sort | Peker, Nesibe |
| collection | NTU |
| description | Parkinson's disease is a neurodegenerative disease characterized by tremors, muscle stiffness, and muscle weakness. Molecular genetic analysis has confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with Parkinson's disease. PARKIN is an E3 ubiquitin ligase that translocates to mitochondria during loss of mitochondrial membrane potential to increase mitophagy. Although muscle dysfunction is noted in Parkinson's disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's disease. In this study, we report that the mitochondrial uncoupler CCCP promotes PINK1/PARKIN-mediated mitophagy in myogenic C2C12 cells. As a result of this excess mitophagy, we show that CCCP treatment of myotubes leads to the development of myotube atrophy in vitro. Surprisingly, we also found that siRNA-mediated knockdown of Parkin results in impaired mitochondrial turnover. In addition, knockdown of Parkin led to myotubular atrophy in vitro. Consistent with these in vitro results, Parkin knockout muscles showed impaired mitochondrial function and smaller myofiber area, suggesting that Parkin function is required for post-natal skeletal muscle growth and development. |
| first_indexed | 2024-10-01T06:43:07Z |
| format | Journal Article |
| id | ntu-10356/138111 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:43:07Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1381112023-02-28T16:56:49Z Loss of Parkin impairs mitochondrial function and leads to muscle atrophy Peker, Nesibe Donipadi, Vinay Sharma, Mridula McFarlane, Craig Kambadur, Ravi School of Biological Sciences Science::Biological sciences Atrophy Mitochondria Parkinson's disease is a neurodegenerative disease characterized by tremors, muscle stiffness, and muscle weakness. Molecular genetic analysis has confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with Parkinson's disease. PARKIN is an E3 ubiquitin ligase that translocates to mitochondria during loss of mitochondrial membrane potential to increase mitophagy. Although muscle dysfunction is noted in Parkinson's disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's disease. In this study, we report that the mitochondrial uncoupler CCCP promotes PINK1/PARKIN-mediated mitophagy in myogenic C2C12 cells. As a result of this excess mitophagy, we show that CCCP treatment of myotubes leads to the development of myotube atrophy in vitro. Surprisingly, we also found that siRNA-mediated knockdown of Parkin results in impaired mitochondrial turnover. In addition, knockdown of Parkin led to myotubular atrophy in vitro. Consistent with these in vitro results, Parkin knockout muscles showed impaired mitochondrial function and smaller myofiber area, suggesting that Parkin function is required for post-natal skeletal muscle growth and development. Accepted version 2020-04-24T06:59:07Z 2020-04-24T06:59:07Z 2018 Journal Article Peker, N., Donipadi, V., Sharma, M., McFarlane, C., & Kambadur, R. (2018). Loss of Parkin impairs mitochondrial function and leads to muscle atrophy. American Journal of Physiology - Cell Physiology, 315(2), C164-C185. doi:10.1152/ajpcell.00064.2017 0363-6143 https://hdl.handle.net/10356/138111 10.1152/ajpcell.00064.2017 29561660 2-s2.0-85051733065 2 315 C164 C185 en American Journal of Physiology - Cell Physiology © 2018 The American Physiological Society. All rights reserved. This paper was published in American Journal of Physiology - Cell Physiology and is made available with permission of The American Physiological Society. application/pdf |
| spellingShingle | Science::Biological sciences Atrophy Mitochondria Peker, Nesibe Donipadi, Vinay Sharma, Mridula McFarlane, Craig Kambadur, Ravi Loss of Parkin impairs mitochondrial function and leads to muscle atrophy |
| title | Loss of Parkin impairs mitochondrial function and leads to muscle atrophy |
| title_full | Loss of Parkin impairs mitochondrial function and leads to muscle atrophy |
| title_fullStr | Loss of Parkin impairs mitochondrial function and leads to muscle atrophy |
| title_full_unstemmed | Loss of Parkin impairs mitochondrial function and leads to muscle atrophy |
| title_short | Loss of Parkin impairs mitochondrial function and leads to muscle atrophy |
| title_sort | loss of parkin impairs mitochondrial function and leads to muscle atrophy |
| topic | Science::Biological sciences Atrophy Mitochondria |
| url | https://hdl.handle.net/10356/138111 |
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