| 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
|
| リソース情報 |
| ショウジョウバエ |
DGRC#118739
DGRC#118740
DGRC#119231 |
