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

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 Drosophila^TTC19KO and in Danio rerio^TTC19KD, as administration of low con

SUBMITTER: Peruzzo R 

PROVIDER: S-EPMC8032734 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature