Fig. 5.

R-loop–mediated mitochondrial genomic instability caused by mtEXO depletion. (A) Visualization of mtDNA replication by EdU incorporation. Cells were incubated with 6 μM aphidicolin for 4 h before incubation with EdU. Nuclei were stained with DAPI. (Scale bar, 10 μm.) (B) Quantification of total EdU granules per cell. (C) Quantification of EdU granule intensities. Red bar represents the mean value for at least three independent experiments for each condition. ****P < 0.0001; **P < 0.01 according to Mann–Whitney U test. AU, arbitrary units. (D) Changes in mtDNA content relative to nuclear DNA (nDNA) in total DNA extracts. Mean value ± SD obtained from at least four independent experiments are represented. (E) Proposed model for the contribution of mtEXO to R-loop homeostasis in mitochondria.