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.
Författare
Simon Stenberg
Göteborgs universitet
Norges miljø- og biovitenskapelige universitet
Jing Li
Université Côte d'Azur
Arne B Gjuvsland
Norges miljø- og biovitenskapelige universitet
Karl Persson
Göteborgs universitet
Erik Demitz-Helin
Göteborgs universitet
Jia Xing Yue
Université Côte d'Azur
Ciaran Gilchrist
Göteborgs universitet
Timmy Ärengård
Göteborgs universitet
Payam Ghiaci
Göteborgs universitet
Lisa Larsson-Berglund
Göteborgs universitet
Martin Zackrisson
Göteborgs universitet
Johanna Höög
Göteborgs universitet
Mikael Molin
Göteborgs universitet
Chalmers, Biologi och bioteknik, Systembiologi
Gianni Liti
Université Côte d'Azur
Stig Omholt
Norges teknisk-naturvitenskapelige universitet
Jonas Warringer
Göteborgs universitet
Ämneskategorier
Evolutionsbiologi
Cellbiologi
Biokemi och molekylärbiologi
Mikrobiologi
Bioinformatik och systembiologi
Genetik
DOI
10.1101/2020.11.20.391110