Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction

Roberta Peruzzo, Samantha Corrà, Roberto Costa, Michele Brischigliaro, Tatiana Varanita, Lucia Biasutto, Chiara Rampazzo, Daniele Ghezzi, Luigi Leanza, Mario Zoratti, Massimo Zeviani, Cristiano Pittà, Carlo Viscomi, Rodolfo Costa and Ildikò Szabò ()
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Roberta Peruzzo: University of Padova
Samantha Corrà: University of Padova
Roberto Costa: University of Padova
Michele Brischigliaro: University of Padova
Tatiana Varanita: University of Padova
Lucia Biasutto: CNR Institute of Neuroscience
Chiara Rampazzo: University of Padova
Daniele Ghezzi: Fondazione IRCCS Istituto Neurologico Carlo Besta
Luigi Leanza: University of Padova
Mario Zoratti: CNR Institute of Neuroscience
Massimo Zeviani: University of Padova
Cristiano Pittà: University of Padova
Carlo Viscomi: University of Padova
Rodolfo Costa: University of Padova
Ildikò Szabò: University of Padova

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22062-x

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DOI: 10.1038/s41467-021-22062-x

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