Mitochondrial and nuclear genomes have to coevolve to ensure the proper functioning of the different mitochondrial complexes that are assembled from peptides encoded by both genomes. Mismatch between these genomes is believed to be strongly selected against due to the consequent impairments of mitochondrial functions and induction of oxidative stress. Here, we used a Drosophila model harboring an incompatibility between a mitochondrial tRNA tyr and its nuclear-encoded mitochondrial tyrosine synthetase to assess the cellular mechanisms affected by this incompatibility and to test the relative contribution of mitonuclear interactions and aging on the expression of impaired phenotypes. Our results show that the mitochondrial tRNA mutation caused a decrease in mitochondrial oxygen consumption in the incompatible nuclear background but no effect with the compatible nuclear background. Mitochondrial DNA copy number increased in the incompatible genotype but that increase failed to rescue mitochondrial functions. The flies harboring mismatch between nuclear and mitochondrial genomes had almost three times the relative mtDNA copy number and fifty percent higher rate of hydrogen peroxide production compared to other genome combinations at 25 days of age. We also found that aging exacerbated the mitochondrial dysfunctions. Our results reveal the tight interactions linking mitonuclear mismatch to mitochondrial dysfunction, mitochondrial DNA regulation, ROS production and aging.

Exposure to solar UVB radiation leads to the formation of the highly mutagenic cyclobutane pyrimidine dimers (CPDs), the DNA damage responsible for mutations found in skin cancer. The frequency of CPD formation and the repair rate of those lesions are two important parameters to determine the probability of UVR-induced mutations. Previous work has shown that chronic irradiation with sublethal doses of UVB radiation (chronic low-dose UVB radiation) leads to the accumulation of residual CPD that persists over time. We have thus investigated the persistence, localization, and consequences on genome stability of those chronic low-dose UVB radiation-induced residual CPDs. We show that chronic low-dose UVB radiation-induced residual CPDs persist on DNA and are diluted via semiconservative replication. They are overrepresented in the heterochromatin and at the TT dipyrimidine sites, and they catalyze the incidence of sister chromatin exchange. Our results shed some light on the impact of chronic UVB radiation exposure on DNA, with a focus on residual CPDs, their distribution, and consequences.

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