論文 - 詳細
| RRC ID | 74776 |
|---|---|
| 著者 | Miozzo F, Valencia-Alarcón EP, Stickley L, Majcin Dorcikova M, Petrelli F, Tas D, Loncle N, Nikonenko I, Bou Dib P, Nagoshi E. |
| タイトル | Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor. |
| ジャーナル | Nat Commun |
| Abstract |
Progressive degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson's disease (PD). Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. We further show that conditional ablation of Nato3, a mouse homolog of Fer2, in differentiated DA neurons causes mitochondrial abnormalities and locomotor impairments in aged mice. Our results reveal the essential and conserved role of Fer2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modeling and treating PD. |
| 巻・号 | 13(1) |
| ページ | 1426 |
| 公開日 | 2022-3-17 |
| DOI | 10.1038/s41467-022-29075-0 |
| PII | 10.1038/s41467-022-29075-0 |
| PMID | 35301315 |
| PMC | PMC8931002 |
| MeSH | Animals Dopaminergic Neurons* / metabolism Mesencephalon / metabolism Mice Parkinson Disease* / genetics Substantia Nigra / metabolism Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 78 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | DGRC#201616 DGRC#202750 |