Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin
| العنوان: | Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin |
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| المؤلفون: | M. Flint Beal, Yingshi Ouyang, Hannes Vogel, Yufeng Yang, Lichuan Yang, Stephan Gehrke, Ji-Wu Wang, Zhinong Huang, Bingwei Lu, Yuzuru Imai |
| المصدر: | Proceedings of the National Academy of Sciences. 103:10793-10798 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Ubiquitin-Protein Ligases, Mutant, PINK1, Biology, Parkin, Animals, Genetically Modified, RNA interference, medicine, Animals, Drosophila Proteins, Humans, Gene Silencing, Neurons, Genetics, Multidisciplinary, Kinase, Muscles, Neurodegeneration, Dopaminergic, Wild type, Parkinson Disease, Biological Sciences, medicine.disease, nervous system diseases, Mitochondria, Cell biology, Drosophila melanogaster, Nerve Degeneration, RNA Interference, Protein Kinases, Signal Transduction |
| الوصف: | Mutations in Pink1 , a gene encoding a Ser/Thr kinase with a mitochondrial-targeting signal, are associated with Parkinson’s disease (PD), the most common movement disorder characterized by selective loss of dopaminergic neurons. The mechanism by which loss of Pink1 leads to neurodegeneration is not understood. Here we show that inhibition of Drosophila Pink1 (dPink1) function results in energy depletion, shortened lifespan, and degeneration of select indirect flight muscles and dopaminergic neurons. The muscle pathology was preceded by mitochondrial enlargement and disintegration. These phenotypes could be rescued by the wild type but not the pathogenic C-terminal deleted form of human Pink1 (hPink1). The muscle and dopaminergic phenotypes associated with dPink1 inactivation show similarity to that seen in parkin mutant flies and could be suppressed by the overexpression of Parkin but not DJ-1. Consistent with the genetic rescue results, we find that, in dPink1 RNA interference (RNAi) animals, the level of Parkin protein is significantly reduced. Together, these results implicate Pink1 and Parkin in a common pathway that regulates mitochondrial physiology and cell survival in Drosophila . |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efe12e03ba5ad0536551d1c5ff2c2afcTest https://doi.org/10.1073/pnas.0602493103Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....efe12e03ba5ad0536551d1c5ff2c2afc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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