PUBLICATION
Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction
- Authors
- Peruzzo, R., Corrà, S., Costa, R., Brischigliaro, M., Varanita, T., Biasutto, L., Rampazzo, C., Ghezzi, D., Leanza, L., Zoratti, M., Zeviani, M., De Pittà, C., Viscomi, C., Costa, R., Szabò, I.
- ID
- ZDB-PUB-210410-5
- Date
- 2021
- Source
- Nature communications 12: 2103 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adenosine Triphosphate/biosynthesis*
- Animals
- Zebrafish
- Mice
- Cell Line
- Humans
- Mitochondrial Proteins/genetics*
- Reactive Oxygen Species/metabolism
- Pyocyanine/metabolism
- Pyocyanine/pharmacology*
- Membrane Potential, Mitochondrial/drug effects
- Membrane Potential, Mitochondrial/physiology
- Electron Transport Complex III/genetics
- Electron Transport Complex III/metabolism*
- Drosophila melanogaster
- Mitochondrial Diseases/drug therapy*
- Mitochondrial Diseases/pathology
- Membrane Proteins/genetics*
- Oxidation-Reduction/drug effects
- Molecular Chaperones/genetics
- Animals, Genetically Modified
- ATPases Associated with Diverse Cellular Activities/genetics
- PubMed
- 33833234 Full text @ Nat. Commun.
Citation
Peruzzo, R., Corrà, S., Costa, R., Brischigliaro, M., Varanita, T., Biasutto, L., Rampazzo, C., Ghezzi, D., Leanza, L., Zoratti, M., Zeviani, M., De Pittà, C., Viscomi, C., Costa, R., Szabò, I. (2021) Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction. Nature communications. 12:2103.
Abstract
Mitochondrial diseases impair oxidative phosphorylation and ATP production, while effective treatment is still lacking. Defective complex III is associated with a highly variable clinical spectrum. We show that pyocyanin, a bacterial redox cycler, can replace the redox functions of complex III, acting as an electron shunt. Sub-μM pyocyanin was harmless, restored respiration and increased ATP production in fibroblasts from five patients harboring pathogenic mutations in TTC19, BCS1L or LYRM7, involved in assembly/stabilization of complex III. Pyocyanin normalized the mitochondrial membrane potential, and mildly increased ROS production and biogenesis. These in vitro effects were confirmed in both DrosophilaTTC19KO and in Danio rerioTTC19KD, as administration of low concentrations of pyocyanin significantly ameliorated movement proficiency. Importantly, daily administration of pyocyanin for two months was not toxic in control mice. Our results point to utilization of redox cyclers for therapy of complex III disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping