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Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation

Authors :
Simon, Stenberg
Jing, Li
Arne B, Gjuvsland
Karl, Persson
Erik, Demitz-Helin
Carles, González Peña
Jia-Xing, Yue
Ciaran, Gilchrist
Timmy, Ärengård
Payam, Ghiaci
Lisa, Larsson-Berglund
Martin, Zackrisson
Silvana, Smits
Johan, Hallin
Johanna L, Höög
Mikael, Molin
Gianni, Liti
Stig W, Omholt
Jonas, Warringer
Source :
eLife. 11
Publication Year :
2021

Abstract

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.

Details

ISSN :
2050084X
Volume :
11
Database :
OpenAIRE
Journal :
eLife
Accession number :
edsair.pmid..........cf5d290b13e99c21c1a3c8bd89daf623