Maternal bias in mouse radiosensitivity: the role of the mitochondrial PTP

This study investigated, at the molecular level, mitochondrial responses to radiation. In three mouse strains, we found the following: (1) mitochondrial response to calcium stress was associated with a strain's susceptibility to γ-radiation; (2) γ-radiation increased this calcium stress response in a dose-responsive manner; (3) the mitochondrial DNA (mtDNA) copy number in the liver of the radiosensitive mouse strain was significantly lower, as compared to that of the radioresistant strain; (4) adenine nucleotide translocase (ANT) mRNA copy numbers were significantly lower in the radiosensitive strain; (5) the F1 offspring (BC/C57M) of radiosensitive females mated with radioresistant males exhibited a significant difference in calcium stress response from that of the radiation-resistant strain, but the reverse cross did not exhibit this difference; and (6) only those mitochondria extracted from the livers of irradiated BC/C57M mice exhibited a heightened calcium stress response. We propose that a genetic change in ANT and a postirradiation change involving either mtDNA-encoded protein replacement or altered mtDNA association fit these data.