{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:40:54Z","timestamp":1785890454148,"version":"3.56.0"},"reference-count":98,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,8,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiomyocytes require the HSP70 (heat shock protein 70) chaperone BiP (binding immunoglobulin protein) to maintain proteostasis in the endoplasmic reticulum (ER) following cardiac stress. The adenylyl transferase FICD (FIC domain protein adenylyl transferase) is increasingly recognized to regulate BiP activity through the posttranslational addition of an adenosine monophosphate moiety to BiP surface residues. However, the physiological impact of FICD\u2010mediated BiP regulation in the context of cardiovascular health is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">We assessed 6\u2010month and 12\u2010month\u2010old wild\u2010type and FICD knockout mice in a transverse aortic constriction hypertrophy paradigm. We determined cardiac function and injury using echocardiography, histological stainings, and biochemical approaches. In complementary assays, we used isolated neonatal wild\u2010type and FICD knockout cardiomyocytes and cardiac fibroblasts to quantitatively assess cell\u2010type specific adaptations in proteostasis and ER stress responses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We find that FICD deficiency prevents pressure overload\u2010associated heart failure, hypertrophy, and fibrosis. At a cellular level, we observe that FICD\u2010mediated BiP AMPylation blunts the induction of the unfolded protein response and impairs BiP interaction with FAM134B, an ER\u2010selective autophagy receptor, thus limiting ER\u2010selective autophagy induction under stress. In contrast, FICD loss significantly increases BiP\u2010dependent unfolded protein response induction and ER\u2010selective autophagy in stressed cardiomyocytes. We also uncover cell type\u2010specific consequences of FICD activity in response to ER stress, positioning FICD as a critical proteostasis regulator in cardiac tissue.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our results highlight a novel regulatory paradigm controlling stress resilience in cardiomyocytes and offer a rationale to consider FICD as a therapeutic target to treat cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.040192","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T10:35:54Z","timestamp":1755513354000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["FICD (FIC Domain Protein Adenylyl Transferase) Deficiency Protects Mice From Hypertrophy\u2010Induced Heart Failure and Promotes BiP (Binding Immunoglobulin Protein) 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