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 size. How the intestinal absorptive area matches physiological nutrient conditions remains unclear. Here, we show that the transcription factor Nuclear Factor Y (NF-Y) plays a role in this process. NF-Y loss of function in ISCs led to high proliferation and cell growth, a phenotype influenced by dietary nutrients. NF-Y loss of function 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 ISCs 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.