mTOR folate sensing links folate availability to trophoblast cell function

Folate deficiency during pregnancy is associated with restricted fetal growth, although the underlying mechanisms are poorly understood. Here we show that mechanistic target of rapamycin (mTOR) functions as a folate sensor in primary human trophoblast (PHT) cells. Folate sensing by mTOR in PHT cells involves both mTOR Complex 1 and 2 and requires the proton‐coupled folate transporter. We report a previously unknown molecular mechanism by which folate regulates trophoblast cell function. Because mTOR is a positive regulator of placental amino acid transport and mitochondrial function, placental mTOR folate sensing may constitute the mechanistic link between maternal folate status and fetal growth. These findings provide new insight into how folate influences human cell physiology and may have implications for our understanding of how altered folate availability causes diseases such as fetal growth restriction, fetal malformations and cancer.