Cell non-autonomous control of autophagy and metabolism by glial cells
Melissa G. Metcalf, Samira Monshietehadi, Arushi Sahay, Jenni Durieux, Ashley E. Frakes, Martina Velichkovska, Cesar Mena, Amelia Farinas, Melissa Sanchez, Andrew Dillin
Abstract
in intestinal cells via neuropeptides. Autophagy, a key regulator of metabolism and aging, has been described as a cell autonomous process. Surprisingly, we find that glial XBP-1s enhances proteostasis and longevity by cell non-autonomously reprogramming organismal lipid metabolism and activating autophagy. Glial XBP-1s regulates the activation of another transcription factor, HLH-30/TFEB, in the intestine. HLH-30 activates intestinal autophagy, increases intestinal lipid catabolism, and upregulates a robust transcriptional program. Our study reveals a novel role for glia in regulating peripheral lipid metabolism, autophagy, and organellar health through peripheral activation of HLH-30 and autophagy.