Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction.
ATPases Associated with Diverse Cellular Activities
/ genetics
Adenosine Triphosphate
/ biosynthesis
Animals
Animals, Genetically Modified
Cell Line
Drosophila melanogaster
Electron Transport Complex III
/ genetics
Humans
Membrane Potential, Mitochondrial
/ drug effects
Membrane Proteins
/ genetics
Mice
Mitochondrial Diseases
/ drug therapy
Mitochondrial Proteins
/ genetics
Molecular Chaperones
/ genetics
Oxidation-Reduction
/ drug effects
Pyocyanine
/ metabolism
Reactive Oxygen Species
/ metabolism
Zebrafish
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 04 2021
08 04 2021
Historique:
received:
20
01
2020
accepted:
25
02
2021
entrez:
9
4
2021
pubmed:
10
4
2021
medline:
23
4
2021
Statut:
epublish
Résumé
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 Drosophila
Identifiants
pubmed: 33833234
doi: 10.1038/s41467-021-22062-x
pii: 10.1038/s41467-021-22062-x
pmc: PMC8032734
doi:
Substances chimiques
BCS1L protein, human
0
LYRM7 protein, human
0
Membrane Proteins
0
Mitochondrial Proteins
0
Molecular Chaperones
0
Reactive Oxygen Species
0
TTC19 protein, human
0
Adenosine Triphosphate
8L70Q75FXE
Pyocyanine
9OQM399341
ATPases Associated with Diverse Cellular Activities
EC 3.6.4.-
Electron Transport Complex III
EC 7.1.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2103Subventions
Organisme : Medical Research Council
ID : MC_UP_1002/1
Pays : United Kingdom
Organisme : MRF
ID : MRF_MRF-155-0002-RG-ZEVIA
Pays : United Kingdom
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