Xbp1 targets canonical UPR^ER and non-canonical pathways in separate tissues to promote longevity.

ABSTRACT: Transcription factors can reprogram gene expression to promote longevity. Here, we investigate the role of Drosophila Xbp1. Xbp1 is activated by splicing of its primary transcript, Xbp1^u, to generate Xbp1^s, a key activator of the endoplasmic reticulum unfolded protein response (UPR^ER). We show that Xbp1^s induces the conical UPR^ER in the gut, promoting longevity from the resident stem cells. In contrast, in the fat body, Xbp1^s does not appear to trigger UPR^ER but alters metabolic gene expression and is still able to extend lifespan. In the fat body, Xbp1^s and dFOXO impinge on the same target genes, including the PGC-1α orthologue Srl, and dfoxo requires Xbp1 to extend l

SUBMITTER: Li M 

PROVIDER: S-EPMC11144730 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature