Atf-6 Regulates Lifespan through ER-Mitochondrial Calcium Homeostasis.

ABSTRACT: Individually, dysfunction of both the endoplasmic reticulum (ER) and mitochondria has been linked to aging, but how communication between these organelles might be targeted to promote longevity is unclear. Here, we provide evidence that, in Caenorhabditis elegans, inhibition of the conserved unfolded protein response (UPR^ER) mediator, activating transcription factor (atf)-6, increases lifespan by modulating calcium homeostasis and signaling to mitochondria. Atf-6 loss confers longevity via downregulation of the ER calcium buffer, calreticulin. ER calcium release via the inositol triphosphate receptor (IP₃R/itr-1) is required for longevity, while IP₃R/itr-1 gain of function is sufficient to extend lifespan. Highlighting coordination between organelles, the m

SUBMITTER: Burkewitz K 

PROVIDER: S-EPMC8030272 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature