Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila
Mutations in the genes for PINK1 and parkin cause Parkinson’s disease. PINK1 and parkin cooperate in the selective autophagic degradation of damaged mitochondria (mitophagy) in cultured cells. However, evidence for their role in mitophagy in vivo is still scarce. Here, we generated a Drosophila mode...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/35878 |
| _version_ | 1818019817814228992 |
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| author | Tom Cornelissen Sven Vilain Katlijn Vints Natalia Gounko Patrik Verstreken Wim Vandenberghe |
| author_facet | Tom Cornelissen Sven Vilain Katlijn Vints Natalia Gounko Patrik Verstreken Wim Vandenberghe |
| author_sort | Tom Cornelissen |
| collection | DOAJ |
| description | Mutations in the genes for PINK1 and parkin cause Parkinson’s disease. PINK1 and parkin cooperate in the selective autophagic degradation of damaged mitochondria (mitophagy) in cultured cells. However, evidence for their role in mitophagy in vivo is still scarce. Here, we generated a Drosophila model expressing the mitophagy probe mt-Keima. Using live mt-Keima imaging and correlative light and electron microscopy (CLEM), we show that mitophagy occurs in muscle cells and dopaminergic neurons in vivo, even in the absence of exogenous mitochondrial toxins. Mitophagy increases with aging, and this age-dependent rise is abrogated by PINK1 or parkin deficiency. Knockdown of the Drosophila homologues of the deubiquitinases USP15 and, to a lesser extent, USP30, rescues mitophagy in the parkin-deficient flies. These data demonstrate a crucial role for parkin and PINK1 in age-dependent mitophagy in Drosophila in vivo. |
| first_indexed | 2024-04-14T07:57:21Z |
| format | Article |
| id | doaj.art-3a7b992f0f33432b804d642094f9efb0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:57:21Z |
| publishDate | 2018-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3a7b992f0f33432b804d642094f9efb02022-12-22T02:05:00ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.35878Deficiency of parkin and PINK1 impairs age-dependent mitophagy in DrosophilaTom Cornelissen0Sven Vilain1Katlijn Vints2Natalia Gounko3Patrik Verstreken4Wim Vandenberghe5https://orcid.org/0000-0002-9758-5062Laboratory for Parkinson Research, Department of Neurosciences, Leuven, BelgiumDepartment of Neurosciences, KU Leuven, Leuven, Belgium; VIB-KU Leuven Center for Brain & Disease Research, Leuven, BelgiumVIB Electron Microscopy Platform and BioImaging Core, Department of Neurosciences, VIB-KU Leuven Center for Brain and Disease Research, KU Leuven, Leuven, BelgiumVIB Electron Microscopy Platform and BioImaging Core, Department of Neurosciences, VIB-KU Leuven Center for Brain and Disease Research, KU Leuven, Leuven, BelgiumDepartment of Neurosciences, KU Leuven, Leuven, Belgium; VIB-KU Leuven Center for Brain & Disease Research, Leuven, BelgiumLaboratory for Parkinson Research, Department of Neurosciences, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, BelgiumMutations in the genes for PINK1 and parkin cause Parkinson’s disease. PINK1 and parkin cooperate in the selective autophagic degradation of damaged mitochondria (mitophagy) in cultured cells. However, evidence for their role in mitophagy in vivo is still scarce. Here, we generated a Drosophila model expressing the mitophagy probe mt-Keima. Using live mt-Keima imaging and correlative light and electron microscopy (CLEM), we show that mitophagy occurs in muscle cells and dopaminergic neurons in vivo, even in the absence of exogenous mitochondrial toxins. Mitophagy increases with aging, and this age-dependent rise is abrogated by PINK1 or parkin deficiency. Knockdown of the Drosophila homologues of the deubiquitinases USP15 and, to a lesser extent, USP30, rescues mitophagy in the parkin-deficient flies. These data demonstrate a crucial role for parkin and PINK1 in age-dependent mitophagy in Drosophila in vivo.https://elifesciences.org/articles/35878Parkinson's diseasemitochondriaautophagyagingUSP15USP30 |
| spellingShingle | Tom Cornelissen Sven Vilain Katlijn Vints Natalia Gounko Patrik Verstreken Wim Vandenberghe Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila eLife Parkinson's disease mitochondria autophagy aging USP15 USP30 |
| title | Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila |
| title_full | Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila |
| title_fullStr | Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila |
| title_full_unstemmed | Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila |
| title_short | Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila |
| title_sort | deficiency of parkin and pink1 impairs age dependent mitophagy in drosophila |
| topic | Parkinson's disease mitochondria autophagy aging USP15 USP30 |
| url | https://elifesciences.org/articles/35878 |
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