Therefore, although we found no reports linking MNGIE syndrome with Hedgehog pathway inhibition, our data clearly demonstrate that deleting Smo in hepatocytes reduced hepatic production of TP and show that loss of TP activity recapitulated the negative effects of Smo deletion on hepatocyte mitochondria, antioxidant defense, oxidative damage, lipotoxicity, and senescence. This evidence concerns the gene TYMP and mitochondrial neurogastrointestinal encephalomyopathy.