Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation
Journal article, 2022
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.
mitochondrial impairment
oxidative stress
mtDNA
genome editing
Author
Simon Stenberg
Norwegian University of Life Sciences
University of Gothenburg
Jing Li
Sun Yat-Sen University
University of Côte d'Azur
Arne B. Gjuvsland
Norwegian University of Life Sciences
Karl Persson
University of Gothenburg
Erik Demitz-Helin
University of Gothenburg
Carles Gonzalez-Pena
University of Gothenburg
Jia Xing Yue
CNRS
Sun Yat-Sen University
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
Silvana Smits
University of Gothenburg
Johan Hallin
University of Gothenburg
Johanna L. Höög
University of Gothenburg
Mikael Molin
University of Gothenburg
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Gianni Liti
CNRS
Stig Omholt
Norwegian University of Science and Technology (NTNU)
Jonas Warringer
University of Gothenburg
eLife
2050084x (eISSN)
Vol. 11 e76095Subject Categories (SSIF 2011)
Cell Biology
Medical Genetics
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
DOI
10.7554/elife.76095
PubMed
35801695