ER-tethered stress sensor CREBH regulates mitochondrial unfolded protein response to maintain energy homeostasis.

ABSTRACT: The Mitochondrial Unfolded Protein Response (UPR^mt), a mitochondria-originated stress response to altered mitochondrial proteostasis, plays important roles in various pathophysiological processes. In this study, we revealed that the endoplasmic reticulum (ER)-tethered stress sensor CREBH regulates UPR^mt to maintain mitochondrial homeostasis and function in the liver. CREBH is enriched in and required for hepatic Mitochondria-Associated Membrane (MAM) expansion induced by energy demands. Under a fasting challenge or during the circadian cycle, CREBH is activated to promote expression of the genes encoding the key enzymes, chaperones, and regulators of UPR^mt in the liver. Activated CREBH, cooperating with peroxisome proliferator-activated receptor α (PPARα),

SUBMITTER: Kim H 

PROVIDER: S-EPMC11626163 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature