Fig. 4: Longitudinal mtDNA deletion profiles in OxPhos deficient SURF1 and Oligo cells. | Communications Biology

Fig. 4: Longitudinal mtDNA deletion profiles in OxPhos deficient SURF1 and Oligo cells.

From: OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases

Fig. 4

a RNAseq gene expression results for all MitoCarta 3.0 pathways, plus all mtDNA genes, and the integrated stress response (ISR: average of ATF4, ATF5, CHOP, GDF15). Values for each pathway are computed from the average expression levels of all genes in each pathway, expressed as the median-centered value relative to the youngest control timepoints for each pathway (rows). Each column represents a single timepoints (n = 3–8) along the lifespan of each donor or treatment condition (n = 3 donors, 3 groups). b Gene expression time course of selected mitochondrial pathways from E, expressed on a Log2 scale relative to the first control timepoint (baseline). c 10 kb long-range PCR product resolved by agarose gel electrophoresis for control fibroblasts cultured up to 166 days (P3 to 31), and passage-matched SURF1 and Oligo-treated cells. d Results from mtDNA sequencing and Eklipse analysis. Each line in the circos plots depicts a deletion burden in control (Donor2) and SURF1 (Patient2) and Oligo-treated (Donor2) cells from two (early and mid-lifespan) representative passages. e Timecourse of the number of unique mtDNA deletions in control, SURF1, and Oligo-treated cells. Deletion counts were estimated with a variant call cutoff of >5% heteroplasmy. f Total deletion burden in cells across 150 days of lifespan. Data are mean ± SEM. **P < 0.01, ***P < 0.001, mixed effects model (fixed effect of Control/SURF1/Oligo group and days grown, random effects of donor or cell line).

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