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
  • Electron Transport Complex III/genetics
  • Electron Transport Complex III/metabolism*
  • Molecular Chaperones/genetics
  • Membrane Proteins/genetics*
  • Animals, Genetically Modified
  • Reactive Oxygen Species/metabolism
  • Membrane Potential, Mitochondrial/drug effects
  • Membrane Potential, Mitochondrial/physiology
  • Zebrafish
  • ATPases Associated with Diverse Cellular Activities/genetics
  • Drosophila melanogaster
  • Humans
  • Cell Line
  • Mitochondrial Diseases/drug therapy*
  • Mitochondrial Diseases/pathology
  • Adenosine Triphosphate/biosynthesis*
  • Animals
  • Oxidation-Reduction/drug effects
  • Mitochondrial Proteins/genetics*
  • Pyocyanine/metabolism
  • Pyocyanine/pharmacology*
  • Mice
(all 22)
PubMed
33833234 Full text @ Nat. Commun.
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
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ia4TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    ttc19MO1-ttc19MRPHLNO
    1 - 1 of 1
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    Fish
    No data available
    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
    1 - 1 of 1
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    Mapping
    No data available
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    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.