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

More information

Latest update

5/16/2023