Mice Deficient In The &Itshmt2&It Gene Have Mitochondria ! Respiration Defects And Are Embryonic Lethal

Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for human Shmt2 and investigated whether they have respiration defects and premature Shmt2-deficient mice showed embryonic lethality after 13.5 days post Shmt2-deficient embryos had respiration defects and retardation of cell growth. Because Shmt2 substantially controls production of N-formylmethionine-tRNA (fMet-tRNA) in mitochondria, its suppression would reduce mitochondrial translation, resulting in expression of the respiration defects in fibroblasts from Shmt2-deficient embryos. These findings support our hypothesis that age-associated respiration defects in fibroblasts of elderly humans are caused not by mtDNA mutations but by epigenetic regulation of nuclear genes including SHMT2.