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Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation
Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration thr...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427111/ https://www.ncbi.nlm.nih.gov/pubmed/35801695 http://dx.doi.org/10.7554/eLife.76095 |
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author | Stenberg, Simon Li, Jing Gjuvsland, Arne B Persson, Karl Demitz-Helin, Erik González Peña, Carles Yue, Jia-Xing Gilchrist, Ciaran Ärengård, Timmy Ghiaci, Payam Larsson-Berglund, Lisa Zackrisson, Martin Smits, Silvana Hallin, Johan Höög, Johanna L Molin, Mikael Liti, Gianni Omholt, Stig W Warringer, Jonas |
author_facet | Stenberg, Simon Li, Jing Gjuvsland, Arne B Persson, Karl Demitz-Helin, Erik González Peña, Carles Yue, Jia-Xing Gilchrist, Ciaran Ärengård, Timmy Ghiaci, Payam Larsson-Berglund, Lisa Zackrisson, Martin Smits, Silvana Hallin, Johan Höög, Johanna L Molin, Mikael Liti, Gianni Omholt, Stig W Warringer, Jonas |
author_sort | Stenberg, Simon |
collection | PubMed |
description | Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease. |
format | Online Article Text |
id | pubmed-9427111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-94271112022-08-31 Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation Stenberg, Simon Li, Jing Gjuvsland, Arne B Persson, Karl Demitz-Helin, Erik González Peña, Carles Yue, Jia-Xing Gilchrist, Ciaran Ärengård, Timmy Ghiaci, Payam Larsson-Berglund, Lisa Zackrisson, Martin Smits, Silvana Hallin, Johan Höög, Johanna L Molin, Mikael Liti, Gianni Omholt, Stig W Warringer, Jonas eLife Cell Biology Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease. eLife Sciences Publications, Ltd 2022-07-08 /pmc/articles/PMC9427111/ /pubmed/35801695 http://dx.doi.org/10.7554/eLife.76095 Text en © 2022, Stenberg et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Stenberg, Simon Li, Jing Gjuvsland, Arne B Persson, Karl Demitz-Helin, Erik González Peña, Carles Yue, Jia-Xing Gilchrist, Ciaran Ärengård, Timmy Ghiaci, Payam Larsson-Berglund, Lisa Zackrisson, Martin Smits, Silvana Hallin, Johan Höög, Johanna L Molin, Mikael Liti, Gianni Omholt, Stig W Warringer, Jonas Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation |
title | Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation |
title_full | Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation |
title_fullStr | Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation |
title_full_unstemmed | Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation |
title_short | Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation |
title_sort | genetically controlled mtdna deletions prevent ros damage by arresting oxidative phosphorylation |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427111/ https://www.ncbi.nlm.nih.gov/pubmed/35801695 http://dx.doi.org/10.7554/eLife.76095 |
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