Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation
Artikel i vetenskaplig tidskrift, 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
Författare
Simon Stenberg
Norges miljø- og biovitenskapelige universitet
Göteborgs universitet
Jing Li
Sun Yat-Sen University
Université Côte d'Azur
Arne B. Gjuvsland
Norges miljø- og biovitenskapelige universitet
Karl Persson
Göteborgs universitet
Erik Demitz-Helin
Göteborgs universitet
Carles Gonzalez-Pena
Göteborgs universitet
Jia Xing Yue
CNRS
Sun Yat-Sen University
Ciaran Gilchrist
Göteborgs universitet
Timmy Ärengård
Göteborgs universitet
PAYAM GHIACI
Göteborgs universitet
Lisa Larsson-Berglund
Göteborgs universitet
Martin Zackrisson
Göteborgs universitet
Silvana Smits
Göteborgs universitet
Johan Hallin
Göteborgs universitet
Johanna L. Höög
Göteborgs universitet
Mikael Molin
Göteborgs universitet
Chalmers, Biologi och bioteknik, Systembiologi
Gianni Liti
CNRS
Stig Omholt
Norges teknisk-naturvitenskapelige universitet
Jonas Warringer
Göteborgs universitet
eLife
2050084x (eISSN)
Vol. 11 e76095Ämneskategorier
Cellbiologi
Medicinsk genetik
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.7554/elife.76095
PubMed
35801695