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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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.
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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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