Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, Norway; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Jing Li
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; Université Côte d’Azur, CNRS, INSERM, IRCAN, Nice, France
Arne B Gjuvsland
Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, Norway
Karl Persson
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Erik Demitz-Helin
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; Université Côte d’Azur, CNRS, INSERM, IRCAN, Nice, France
Ciaran Gilchrist
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Timmy Ärengård
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Payam Ghiaci
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Lisa Larsson-Berglund
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Martin Zackrisson
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Silvana Smits
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Johan Hallin
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
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.
