دورية أكاديمية
Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction
| العنوان: | Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction |
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| المؤلفون: | 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., Szabo I. |
| المساهمون: | R. Peruzzo, S. Corrà, R. Costa, M. Brischigliaro, T. Varanita, L. Biasutto, C. Rampazzo, D. Ghezzi, L. Leanza, M. Zoratti, M. Zeviani, C. De Pittà, C. Viscomi, I. Szabo |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2021 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | ATPases associated with diverse cellular activitie, adenosine triphosphate, animal, animals, genetically modified, cell line, drosophila melanogaster, electron transport complex III, human, membrane potential, mitochondrial, membrane protein, mice, mitochondrial disease, mitochondrial protein, molecular chaperone, oxidation-reduction, pyocyanine, reactive oxygen specie, zebrafish, Settore MED/03 - Genetica Medica |
| الوصف: | Mitochondrial diseases impair oxidative phosphorylation and ATP production, while effective treatment is still lacking. Defective complex III is associated with ahighly 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33833234; info:eu-repo/semantics/altIdentifier/wos/WOS:000639205600002; volume:12; issue:1; firstpage:1; lastpage:19; numberofpages:19; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/2434/863426Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85104085016 |
| DOI: | 10.1038/s41467-021-22062-x |
| الإتاحة: | https://doi.org/10.1038/s41467-021-22062-xTest http://hdl.handle.net/2434/863426Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B8481234 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-021-22062-x |
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