Control of mitochondrial superoxide production includes programmed mtDNA deletion and restoration
Preprint, 2020
Deletion of mitochondrial DNA in eukaryotes is mainly 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 the regulatory circuitry underlying this editing critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication. 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. Our results may therefore be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.One-Sentence SummaryGenetically controlled editing of mitochondrial DNA is an integral part of the yeast’s defenses against oxidative damage.
Author
Simon Stenberg
University of Gothenburg
Norwegian University of Life Sciences
Jing Li
University of Côte d'Azur
Arne B Gjuvsland
Norwegian University of Life Sciences
Karl Persson
University of Gothenburg
Erik Demitz-Helin
University of Gothenburg
Jia Xing Yue
University of Côte d'Azur
Ciaran Gilchrist
University of Gothenburg
Timmy Ärengård
University of Gothenburg
Payam Ghiaci
University of Gothenburg
Lisa Larsson-Berglund
University of Gothenburg
Martin Zackrisson
University of Gothenburg
Johanna Höög
University of Gothenburg
Mikael Molin
University of Gothenburg
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Gianni Liti
University of Côte d'Azur
Stig Omholt
Norwegian University of Science and Technology (NTNU)
Jonas Warringer
University of Gothenburg
Subject Categories
Evolutionary Biology
Cell Biology
Biochemistry and Molecular Biology
Microbiology
Bioinformatics and Systems Biology
Genetics
DOI
10.1101/2020.11.20.391110