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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Bibliographic Details
Published in:	eLife Vol. 11
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 08-07-2022 eLife Sciences Publications, Ltd eLife Sciences Publications Ltd
Subjects:	Cell Biology Cellbiologi Cells DNA DNA Damage DNA, Mitochondrial - genetics DNA, Mitochondrial - metabolism Enzymes Evolutionary Biology Evolutionsbiologi Genes Genetics Genetics and Genomics Genetik genome editing genome stability Humans metabolism Mitochondria Mitochondria - metabolism Mitochondrial Mitochondrial DNA mitochondrial impairment mtDNA Oxidative Phosphorylation Oxidative Stress Oxidative Stress - genetics Reactive Oxygen Species Reactive Oxygen Species - metabolism Superoxide Superoxides Superoxides - metabolism genome editing genome stability cell biology genetics mitochondrial DNA mitochondrial impairment genomics oxidative stress S. cerevisiae
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.76095