The mammalian mitochondrial genome (mtDNA) is multicopy and its copy number
(mtCN) varies widely across tissues, in development and in disease. Here, we system-
atically 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 mito-
chondrial 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.