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Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects
Omaveloxolone (RTA408) is a second-generation oleanane triterpenoid Nrf2 inducer with antioxidant and anti-inflammatory properties and was reported to improve mitochondrial bioenergetics. It is currently being tested in medical trials for Friedrich ataxia, a genetic, multi-organ disease involving mi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411646/ https://www.ncbi.nlm.nih.gov/pubmed/36032663 http://dx.doi.org/10.3389/fmolb.2022.890653 |
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author | Zighan, Madleen Arkadir, David Douiev, Liza Keller, Guy Miller, Chaya Saada, Ann |
author_facet | Zighan, Madleen Arkadir, David Douiev, Liza Keller, Guy Miller, Chaya Saada, Ann |
author_sort | Zighan, Madleen |
collection | PubMed |
description | Omaveloxolone (RTA408) is a second-generation oleanane triterpenoid Nrf2 inducer with antioxidant and anti-inflammatory properties and was reported to improve mitochondrial bioenergetics. It is currently being tested in medical trials for Friedrich ataxia, a genetic, multi-organ disease involving mitochondrial dysfunction. Thus, omaveloxolone could potentially be beneficial for additional disorders involving mitochondrial dysfunction. To this end, we investigated its effect on primary fibroblasts derived from patients with mitochondrial complex I deficiency, mitochondrial cytochrome oxidase deficiency, and two recessive forms of Parkinson’s disease. Patients and control cells were incubated in the presence or absence of 50 nM omaveloxolone for 72 h prior to measurements. Generally, growth on galactose medium and ATP production were unaltered. Mitochondrial membrane potential was slightly but significantly decreased, while reactive oxygen species (ROS) production was variably decreased. Mitochondrial mass and mitochondrial DNA (mtDNA) contents were significantly increased in the patient’s cells. These results were partially confirmed by the results of oxygen consumption studies which disclosed increased maximal oxygen consumption rates in most cells and increased energy status in all treated cells. Further investigation is required to explore the precise effect of omaveloxolone on mitochondrial function in disease. |
format | Online Article Text |
id | pubmed-9411646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94116462022-08-27 Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects Zighan, Madleen Arkadir, David Douiev, Liza Keller, Guy Miller, Chaya Saada, Ann Front Mol Biosci Molecular Biosciences Omaveloxolone (RTA408) is a second-generation oleanane triterpenoid Nrf2 inducer with antioxidant and anti-inflammatory properties and was reported to improve mitochondrial bioenergetics. It is currently being tested in medical trials for Friedrich ataxia, a genetic, multi-organ disease involving mitochondrial dysfunction. Thus, omaveloxolone could potentially be beneficial for additional disorders involving mitochondrial dysfunction. To this end, we investigated its effect on primary fibroblasts derived from patients with mitochondrial complex I deficiency, mitochondrial cytochrome oxidase deficiency, and two recessive forms of Parkinson’s disease. Patients and control cells were incubated in the presence or absence of 50 nM omaveloxolone for 72 h prior to measurements. Generally, growth on galactose medium and ATP production were unaltered. Mitochondrial membrane potential was slightly but significantly decreased, while reactive oxygen species (ROS) production was variably decreased. Mitochondrial mass and mitochondrial DNA (mtDNA) contents were significantly increased in the patient’s cells. These results were partially confirmed by the results of oxygen consumption studies which disclosed increased maximal oxygen consumption rates in most cells and increased energy status in all treated cells. Further investigation is required to explore the precise effect of omaveloxolone on mitochondrial function in disease. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9411646/ /pubmed/36032663 http://dx.doi.org/10.3389/fmolb.2022.890653 Text en Copyright © 2022 Zighan, Arkadir, Douiev, Keller, Miller and Saada. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Zighan, Madleen Arkadir, David Douiev, Liza Keller, Guy Miller, Chaya Saada, Ann Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects |
title | Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects |
title_full | Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects |
title_fullStr | Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects |
title_full_unstemmed | Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects |
title_short | Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects |
title_sort | variable effects of omaveloxolone (rta408) on primary fibroblasts with mitochondrial defects |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411646/ https://www.ncbi.nlm.nih.gov/pubmed/36032663 http://dx.doi.org/10.3389/fmolb.2022.890653 |
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