PUBLICATION
In vivo detection of mitochondrial dysfunction induced by clinical drugs and disease-associated genes using a novel dye ZMJ214 in zebrafish
- Authors
- Sasagawa, S., Nishimura, Y., Koiwa, J., Nomoto, T., Shinto, T., Murakami, S., Yuge, M., Kawaguchi, K., Kawase, R., Miyazaki, T., Tanaka, T.
- ID
- ZDB-PUB-151204-7
- Date
- 2016
- Source
- ACS Chemical Biology 11(2): 381-8 (Journal)
- Registered Authors
- Tanaka, Toshio
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/toxicity
- Anticonvulsants/toxicity
- Benzophenones/toxicity
- Carbocyanines/chemistry*
- Chromans/toxicity
- Disease Models, Animal
- Fluorescent Dyes/chemistry*
- Hypoglycemic Agents/toxicity
- Membrane Potential, Mitochondrial/drug effects*
- Mitochondria/drug effects*
- Mitochondria/pathology*
- Nitrophenols/toxicity
- Oligomycins/toxicity
- Optical Imaging*/methods
- Thiazolidinediones/toxicity
- Toxicity Tests/methods
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- PubMed
- 26630578 Full text @ ACS Chem. Biol.
Citation
Sasagawa, S., Nishimura, Y., Koiwa, J., Nomoto, T., Shinto, T., Murakami, S., Yuge, M., Kawaguchi, K., Kawase, R., Miyazaki, T., Tanaka, T. (2016) In vivo detection of mitochondrial dysfunction induced by clinical drugs and disease-associated genes using a novel dye ZMJ214 in zebrafish. ACS Chemical Biology. 11(2):381-8.
Abstract
Mitochondrial dysfunction has been implicated in various drug-induced toxicities and genetic disorders. Recently, zebrafish has emerged as a versatile animal model for both chemical and genetic screenings. Taking advantage of its transparency, various in vivo fluorescent imaging methods have been developed to identify novel functions of chemicals and genes in zebrafish. However, there have not been fluorescent probes that can detect mitochondrial membrane potential in living zebrafish. In this study, we identified a novel cyanine dye called ZMJ214 that detects mitochondrial membrane potential in living zebrafish from 4 to 8 days post fertilization and is administered by simple immersion. The fluorescence intensity of ZMJ214 in zebrafish were increased and decreased by oligomycin and FCCP, respectively, suggesting a positive correlation between ZMJ214 fluorescence and mitochondrial membrane potential. In vivo imaging of zebrafish stained with ZMJ214 allowed for the detection of altered mitochondrial membrane potential induced by the anti-diabetic drug troglitazone and the anti-epileptic drug tolcapone, both of which have been withdrawn from the market due to mitochondrial toxicity. In contrast, pioglitazone and entacapone, which are similar to troglitazone and tolcapone, respectively, and have been used commercially, did not cause a change in mitochondrial membrane potential in zebrafish stained with ZMJ214. Live imaging of zebrafish stained with ZMJ214 also revealed that knock-down of slc25a12, a mitochondrial carrier protein associated with autism, dysregulated mitochondrial membrane potential. These results suggest that ZMJ214 can be a useful tool to identify chemicals and genes that cause mitochondrial dysfunction in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping