RRC ID 71789
Author Imai Y, Inoshita T, Meng H, Shiba-Fukushima K, Hara KY, Sawamura N, Hattori N.
Title Light-driven activation of mitochondrial proton-motive force improves motor behaviors in a Drosophila model of Parkinson's disease.
Journal 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.
Volume 2
Pages 424
Published 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
Drosophila DGRC#118739 DGRC#118740