Extended Data Fig. 5. Widespread mitochondrial clearance suppresses inflammation during senescence, while reintroduction of mtDNA restored it.
(a) Column clustered heatmap of SASP genes that are differentially expressed in senescent IMR90 fibroblasts, down-regulated upon mitochondria clearance and are rescued by mtDNA transfection. The colour intensity represents column Z-score, where red and blue indicate high and low expression, respectively. (b) Gene members of two hallmark signatures, TNFA-signalling via NFKB (M5890) and Hecker IFNB1 targets (M3010), were upregulated in senescent cells and downregulated after CCCP. Subsequent addition of mtDNA rescued this phenotype. (c) The GSEA plots for Parkin Sen vs. Parkin Prol display an enrichment for the TNFA-signalling via NF-κB (M5890) and Hecker IFNB1 targets (M3010) pathways in the senescent cell population. Addition of mtDNA led to a significant enrichment compared to CCCP alone in senescent cells. (d) Venn diagram depicting a substantial overlap of enriched pathways in all three conditions (FWER p-value < 0.25).