Mitochondrial genome copy number variation across tissues in mice and humans

The mammalian mitochondrial genome (mtDNA) is multicopy and its copy number (mtCN) varies widely across tissues, in development and in disease. Here, we systematically catalog this variation by assaying mtCN in 52 human tissues across 952 donors (10,499 samples from the Genotype- Tissue Expression project) and 20 murine tissues using qPCR, capturing 50- and 200- fold variation, respectively. We also estimate per cell mtCN across 173 human cell lines from the Cancer Cell Line Encyclopedia using whole- genome sequencing data and observe >50- fold variation. We then leverage the vast amount of genomics data available for these repositories to credential our resource and uncover mtDNA- related biology. Using already existing proteomics data, we show that variation in mtCN can be predicted by variation in TFAM, histone, and mitochondrial ribosome protein abundance. We also integrate mtCN estimates with the CRISPR gene dependency measurements to find that cell lines with high mtCN are resistant to loss of GPX4, a glutathione phospholipid hydroperoxidase. Our resource captures variation in mtCN across mammalian tissues and should be broadly useful to the research community.