Calcium signaling at the endoplasmic reticulum: fine-tuning stress responses

Endoplasmic reticulum (ER) calcium signaling is implicated in a myriad of coordinated cellular processes. The ER calcium content is tightly regulated as it allows a favorable environment for protein folding, in addition to operate as a major reservoir for fast and specific release of calcium. Altered ER homeostasis impacts protein folding, activating the unfolded protein response (UPR) as a rescue mechanism to restore proteostasis. ER calcium release impacts mitochondrial metabolism and also fine-tunes the threshold to undergo apoptosis under chronic stress. The global coordination between UPR signaling and energetic demands takes place at mitochondrial associated membranes (MAMs), specialized subdomains mediating interorganelle communication. Here we discuss current models explaining the functional relationship between ER homeostasis and various cellular responses to coordinate proteostasis and metabolic maintenance.FONDECYT 1140549 3150113 FONDAP program 15150012 Millennium Institute P09-015-F European Commission R D, MSCA-RISE 734749 ALS Therapy Alliance 2014-F-059 Muscular Dystrophy Association 382453 Michael J Fox Foundation for Parkinson Research-Target Validation grant 9277 CONICYT-Brazil 441921/2016-7 US Office of Naval Research-Global (ONR-G) N62909-16-1-2003 U.S. Air Force Office of Scientific Research FA9550-16-1-0384 FONDEF 16I10223 D11E1007 ALSRP Therapeutic Idea Award AL15011