Bag3 Regulates Mitochondrial Function and the Inflammasome Through Canonical and Noncanonical Pathways in the Heart

B-cell lymphoma 2-associated athanogene-3 (Bag3) is expressed in all animal species, with Bag3 levels being most prominent in the heart, the skeletal muscle, the central nervous system, and in many cancers. Preclinical studies of Bag3 biology have focused on animals that have developed compromised cardiac function; however, the present studies were performed to identify the pathways perturbed in the heart even before the occurrence of clinical signs of dilatation and failure of the heart. These studies show that hearts carrying variants that knockout one allele of BAGS have significant alterations in multiple cellular pathways including apoptosis, autophagy, mitochondrial homeostasis, and the inflammasome. (J Am Coll Cardiol Basic Trans Science 2023;8:820-839) & COPY; 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Bag3 is widely expressed in various animal species, with higher levels observed in the heart, skeletal muscle, central nervous system, and many cancers. Studies show that hearts carrying alleles with one knockout of BAGS exhibit significant changes in multiple cellular pathways, such as apoptosis, autophagy, mitochondrial homeostasis, and the inflammasome, even before clinical signs of dilatation and heart failure occur.