Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson’s disease

Yuzuru Imai*, Tsuyoshi Inoshita, Hongrui Meng, Kahori Shiba-Fukushima, Kiyotaka Y. Hara, Naoya Sawamura, Nobutaka Hattori

*この研究の対応する著者

研究成果査読

10 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号424
ジャーナルCommunications Biology
2
1
DOI
出版ステータスPublished - 2019 12 1

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 医学(その他)

フィンガープリント

「Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson’s disease」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル