論文 - 詳細
| RRC ID | 71789 |
|---|---|
| 著者 | Imai Y, Inoshita T, Meng H, Shiba-Fukushima K, Hara KY, Sawamura N, Hattori N. |
| タイトル | Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson's disease. |
| ジャーナル | Commun Biol |
| Abstract |
Mitochondrial degeneration is considered one of the major causes of Parkinson's disease (PD). Improved mitochondrial functions are expected to be a promising therapeutic strategy for PD. In this study, we introduced a light-driven proton transporter, Delta-rhodopsin (dR), to Drosophila mitochondria, where the mitochondrial proton-motive force (Δp) and mitochondrial membrane potential are maintained in a light-dependent manner. The loss of the PD-associated mitochondrial gene CHCHD2 resulted in reduced ATP production, enhanced mitochondrial peroxide production and lower Ca2+-buffering activity in dopaminergic (DA) terminals in flies. These cellular defects were improved by the light-dependent activation of mitochondrion-targeted dR (mito-dR). Moreover, mito-dR reversed the pathology caused by the CHCHD2 deficiency to suppress α-synuclein aggregation, DA neuronal loss, and elevated lipid peroxidation in brain tissue, improving motor behaviors. This study suggests the enhancement of Δp by mito-dR as a therapeutic mechanism that ameliorates neurodegeneration by protecting mitochondrial functions. |
| 巻・号 | 2 |
| ページ | 424 |
| 公開日 | 2019-1-1 |
| DOI | 10.1038/s42003-019-0674-1 |
| PII | 674 |
| PMID | 31799427 |
| PMC | PMC6874642 |
| MeSH | Animals Biomarkers Disease Models, Animal Disease Susceptibility Dopaminergic Neurons / metabolism Drosophila Light* Mitochondria / metabolism* Mitochondria / radiation effects* Mitochondrial Diseases / etiology* Mitochondrial Diseases / metabolism* Models, Biological Motor Activity* Oxidative Stress Parkinson Disease / etiology* Parkinson Disease / metabolism* Protons* Reactive Oxygen Species / metabolism alpha-Synuclein / metabolism |
| IF | 4.165 |
| 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 | 36 |
| 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#118739 DGRC#118740 DGRC#119231 |