Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos

Mitochondrial DNA (mtDNA) mutator mice express proofreading-deficient mtDNA polymerase gamma (Polg D257A ) and age prematurely 1,2 , whereas mice with other mitochondrial defects do not show global signs of early aging. The reason for this discrepancy is not completely understood. Hämäläinen et al. recently reported that both induced pluripotent stem cells (iPSCs) and primary mutator embryonic fibroblasts harboring Polg D257A demonstrate increased mtDNA replication frequency leading to depletion of the total cellular dNTP pool 3 . The authors proposed that the decreased availability of cellular dNTPs for nuclear genome replication leads to compromised nuclear genome maintenance and premature aging. Here we report that total cellular dNTP pools are normal in mtDNA mutator mouse embryos (genotype: Polg D257A/D257A ), which shows that a living organism exclusively expressing Polg D257A has normal total dNTP pools despite ubiquitous rapid cell division.