Nuclear Factor Y controls nutrient-adaptive epithelial growth by regulating mTOR in the Drosophila midgut

The intestinal epithelial lining is highly dynamic, with size and cellular composition adapting to nutrient status. This requires regulation of intestinal stem cell (ISC) proliferation and enterocyte (EC) size. How the intestinal absorptive area matches physiological nutrient conditions remains unclear. Here, we show that the Nuclear Factor Y (NF-Y) transcription factor plays a role in this process. NF-Y loss-of-function (LOF) in ISCs led to high proliferation and cell growth, a phenotype influenced by dietary nutrients. NF-Y LOF also increased nutrient metabolism, as shown by more mitochondria and larger lipid droplets in progenitors. Mechanistically, NF-Y restrains mTOR complex 1 (mTORC1) activity in ISC by controlling transcription of mTORC1 signaling components such as Pras40 and Sestrin. Overall, our results demonstrate that NF-Y limits excessive nutrient-adaptive intestinal epithelial growth.