Details

Autor(en) / Beteiligte

• Metcalf, Melissa G.
• Monshietehadi, Samira
• Sahay, Arushi
• Durieux, Jenni
• Frakes, Ashley E.
• Velichkovska, Martina
• Mena, Cesar
• Farinas, Amelia
• Sanchez, Melissa
• Dillin, Andrew

Titel

Cell non-autonomous control of autophagy and metabolism by glial cells

Ist Teil von

• iScience, 2024-04, Vol.27 (4), p.109354-109354, Article 109354

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Glia are the protectors of the nervous system, providing neurons with support and protection from cytotoxic insults. We previously discovered that four astrocyte-like glia can regulate organismal proteostasis and longevity in C. elegans. Expression of the UPRER transcription factor, XBP-1s, in these glia increases stress resistance, and longevity, and activates the UPRER 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. [Display omitted] •Glial XBP-1s reduces peripheral lipids, boosts autophagy, and changes ER structure•Glial XBP-1s regulates the activation of HLH-30 in the intestine•Lipid depletion and lifespan extension phenotypes are dependent on hlh-30•Macroautophagy genes are required for longevity and altered ER structure Biological sciences; Neuroscience; Cell biology; Functional aspects of cell biology