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Here, we demonstrate that TRIC-A is essential for maintaining balanced SR Ca2+ release, mitochondrial integrity, and cardiac resilience during \u03b2-adrenergic stimulation. Tric-a\u2212\/\u2212 cardiomyocytes exhibited Ca2+ transients evoked by electrical stimuli and exaggerated isoproterenol (ISO)-evoked Ca2+ release, consistent with SR Ca2+ overload. These defects were accompanied by selective upregulation of protein kinase A (PKA)-dependent phosphorylation of ryanodine receptor 2 (RyR2) (S2808) and phospholamban (PLB) (S16). Acute ISO challenge induced mitochondrial swelling, cristae disruption, and Evans Blue Dye uptake, and elevated circulating troponin T in Tric-a\u2212\/\u2212 hearts, hallmarks of necrosis-like cell death. Mitochondrial Ca2+ uptake inhibition with Ru360 markedly reduced membrane injury, establishing mitochondrial Ca2+ overload as the proximal trigger of cardiac cell death. With sustained \u03b2-adrenergic stimulation by ISO, Tric-a\u2212\/\u2212 hearts developed extensive interstitial and perivascular fibrosis without exaggerated hypertrophy. Cardiac fibroblasts lacked TRIC-A expression and displayed normal Ca2+ signaling and activation, indicating that fibrosis arises secondarily from cardiomyocyte injury rather than fibroblast-intrinsic abnormalities. These findings identify TRIC-A as a critical regulator of SR-mitochondrial Ca2+ coupling and a key molecular safeguard that protects the heart from catecholamine-induced injury and maladaptive remodeling.<\/jats:p>","DOI":"10.3390\/biom16020181","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:52:38Z","timestamp":1769190758000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TRIC-A Loss Sensitizes the Heart to \u03b2-Adrenergic Stress and Drives Cardiomyocyte Death and Fibrosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6193-9826","authenticated-orcid":false,"given":"Ki Ho","family":"Park","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Surgical Sciences, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiju","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Research Unit for Physiological Chemistry, the Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8502, Japan"},{"name":"Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan"},{"name":"Division of Pharmacology, National Institute of Health Sciences, Kawasaki 210-9501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Sciences, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Komazaki","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Saitama Medical University, Saitama 350-0495, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7957-5381","authenticated-orcid":false,"given":"Chengzhu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Nishi","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingsong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, University of Texas at Arlington, Arlington, TX 76010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Takeshima","sequence":"additional","affiliation":[{"name":"Research Unit for Physiological Chemistry, the Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8502, Japan"},{"name":"Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Sciences, University of Virginia, Charlottesville, VA 22903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/415198a","article-title":"Cardiac excitation-contraction coupling","volume":"415","author":"Bers","year":"2002","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"H348","DOI":"10.1152\/ajpheart.00227.2025","article-title":"Excitation-contraction coupling, cardiomyocyte electrophysiology, and transcriptome profiles in two HFpEF murine models: Etiology and sex-dependent differences","volume":"330","author":"Hegyi","year":"2026","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1161\/CIRCULATIONAHA.125.073937","article-title":"Junctophilin-2 Regulates Store-Operated Calcium Entry to Drive Cardiac Fibroblast Activation, Fibrotic Repair, and Angiogenesis After Myocardial Infarction","volume":"152","author":"Wang","year":"2025","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2519545","DOI":"10.1080\/19336950.2025.2519545","article-title":"Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies","volume":"19","author":"Wang","year":"2025","journal-title":"Channels"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pbiomolbio.2020.02.008","article-title":"Cardiomyocyte calcium handling in health and disease: Insights from in vitro and in silico studies","volume":"157","author":"Sutanto","year":"2020","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mattiazzi, A., Jaquenod De Giusti, C., and Valverde, C.A. (2025). CaMKII at the crossroads: Calcium dysregulation, and post-translational modifications driving cell death. J. Physiol., 1\u201317.","DOI":"10.1113\/JP285941"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1161\/CIRCRESAHA.117.310230","article-title":"Calcium and Excitation-Contraction Coupling in the Heart","volume":"121","author":"Eisner","year":"2017","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1113\/JP281482","article-title":"Local recovery of cardiac calcium-induced calcium release interrogated by ultra-effective, two-photon uncaging of calcium","volume":"599","author":"Janicek","year":"2021","journal-title":"J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00424-020-02506-x","article-title":"Excitation-contraction coupling and calcium release in atrial muscle","volume":"473","author":"Blatter","year":"2021","journal-title":"Pflug. Arch."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Marchena, M., and Echebarria, B. (2020). Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231056"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/BF00583791","article-title":"Ca2+-movements in muscle modulated by the state of K+-channels in the sarcoplasmic reticulum membranes","volume":"409","author":"Fink","year":"1987","journal-title":"Pflug. Arch."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.yjmcc.2016.10.018","article-title":"Sarcoplasmic reticulum Ca2+, Mg2+, K+, and Cl\u2212 concentrations adjust quickly as heart rate changes","volume":"103","author":"Berti","year":"2017","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nature05928","article-title":"TRIC channels are essential for Ca2+ handling in intracellular stores","volume":"448","author":"Yazawa","year":"2007","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/cr.2016.140","article-title":"Crystal structures of the TRIC trimeric intracellular cation channel orthologues","volume":"26","author":"Kasuya","year":"2016","journal-title":"Cell Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cmet.2011.05.011","article-title":"TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance","volume":"14","author":"Yamazaki","year":"2011","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.bpj.2017.11.3775","article-title":"Sarcoplasmic Reticulum Ca2+ Release Uses a Cascading Network of Intra-SR and Channel Countercurrents","volume":"114","author":"Zsolnay","year":"2018","journal-title":"Biophys. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dong, M., and Maturana, A.D. (2025). Effects of aging on calcium channels in skeletal muscle. Front. Mol. Biosci., 12.","DOI":"10.3389\/fmolb.2025.1558456"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1242\/dev.036798","article-title":"Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation","volume":"136","author":"Yamazaki","year":"2009","journal-title":"Development"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1161\/CIRCRESAHA.119.316241","article-title":"TRIC-A Channel Maintains Store Calcium Handling by Interacting with Type 2 Ryanodine Receptor in Cardiac Muscle","volume":"126","author":"Zhou","year":"2020","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00424-021-02513-6","article-title":"TRIC-A regulates intracellular Ca2+ homeostasis in cardiomyocytes","volume":"473","author":"Zhou","year":"2021","journal-title":"Pflug. Arch."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37370","DOI":"10.1074\/jbc.M110.170084","article-title":"Ca2+ overload and sarcoplasmic reticulum instability in tric-a null skeletal muscle","volume":"285","author":"Zhao","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cabral, W.A., Ishikawa, M., Garten, M., Makareeva, E.N., Sargent, B.M., Weis, M., Barnes, A.M., Webb, E.A., Shaw, N.J., and Ala-Kokko, L. (2016). Absence of the ER Cation Channel TMEM38B\/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006156"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/jhg.2016.11","article-title":"Two novel mutations in TMEM38B result in rare autosomal recessive osteogenesis imperfecta","volume":"61","author":"Lv","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_24","first-page":"582","article-title":"A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta","volume":"34","author":"Volodarsky","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.gene.2014.05.028","article-title":"A novel deletion mutation involving TMEM38B in a patient with autosomal recessive osteogenesis imperfecta","volume":"545","author":"Rubinato","year":"2014","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1136\/jmedgenet-2012-101142","article-title":"Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation","volume":"49","author":"Shaheen","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.molcel.2016.04.035","article-title":"Tissue-Specific Gene Repositioning by Muscle Nuclear Membrane Proteins Enhances Repression of Critical Developmental Genes during Myogenesis","volume":"62","author":"Robson","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102587","DOI":"10.1016\/j.ebiom.2019.11.048","article-title":"A multistage sequencing strategy pinpoints novel candidate alleles for Emery-Dreifuss muscular dystrophy and supports gene misregulation as its pathomechanism","volume":"51","author":"Meinke","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.nmd.2016.12.003","article-title":"Immunohistochemistry on a panel of Emery-Dreifuss muscular dystrophy samples reveals nuclear envelope proteins as inconsistent markers for pathology","volume":"27","author":"Meinke","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13062","DOI":"10.1073\/pnas.0402388101","article-title":"RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR)","volume":"101","author":"Jiang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/oxfordjournals.jbchem.a123735","article-title":"Phosphorylation of ryanodine receptors in rat myocytes during beta-adrenergic stimulation","volume":"111","author":"Yoshida","year":"1992","journal-title":"J. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"De Lucia, C., Eguchi, A., and Koch, W.J. (2018). New Insights in Cardiac beta-Adrenergic Signaling During Heart Failure and Aging. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00904"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"H665","DOI":"10.1152\/ajpheart.00467.2011","article-title":"Catecholamine-induced cardiac mitochondrial dysfunction and mPTP opening: Protective effect of curcumin","volume":"302","author":"Djerdjouri","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e77725","DOI":"10.7554\/eLife.77725","article-title":"Prolonged beta-adrenergic stimulation disperses ryanodine receptor clusters in cardiomyocytes and has implications for heart failure","volume":"11","author":"Shen","year":"2022","journal-title":"eLife"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15103","DOI":"10.1038\/ncomms15103","article-title":"Structural basis for conductance through TRIC cation channels","volume":"8","author":"Su","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature19767","article-title":"Pore architecture of TRIC channels and insights into their gating mechanism","volume":"538","author":"Yang","year":"2016","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ou, X., Guo, J., Wang, L., Yang, H., Liu, X., Sun, J., and Liu, Z. (2017). Ion- and water-binding sites inside an occluded hourglass pore of a trimeric intracellular cation (TRIC) channel. BMC Biol., 15.","DOI":"10.1186\/s12915-017-0372-8"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1073\/pnas.1817271116","article-title":"Structural basis for activity of TRIC counter-ion channels in calcium release","volume":"116","author":"Wang","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, A., Zhou, X., Park, K.H., Yi, J., Li, X., Ko, J.K., Chen, Y., Nishi, M., Yamazaki, D., and Takeshima, H. (2025). TRIC-A Facilitates Sarcoplasmic Reticulum-Mitochondrial Ca2+ Signaling Crosstalk in Cardiomyocytes. Cells, 14.","DOI":"10.3390\/cells14201579"},{"key":"ref_40","first-page":"e4412","article-title":"Protocol for Isolation of Cardiomyocyte from Adult Mouse and Rat","volume":"12","author":"Zhang","year":"2022","journal-title":"Bio Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nature11044","article-title":"In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes","volume":"485","author":"Qian","year":"2012","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.yjmcc.2012.03.015","article-title":"PKA phosphorylation of cardiac ryanodine receptor modulates SR luminal Ca2+ sensitivity","volume":"53","author":"Ullrich","year":"2012","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1113\/JP286453","article-title":"Dual ablation of the RyR2-Ser2808 and RyR2-Ser2814 sites increases propensity for pro-arrhythmic spontaneous Ca2+ releases","volume":"602","author":"Janicek","year":"2024","journal-title":"J. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.yjmcc.2016.06.007","article-title":"CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift","volume":"98","author":"Uchinoumi","year":"2016","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9627","DOI":"10.1111\/jcmm.15470","article-title":"CaMKII-dependent ryanodine receptor phosphorylation mediates sepsis-induced cardiomyocyte apoptosis","volume":"24","author":"Sepulveda","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.yjmcc.2025.01.004","article-title":"RyR2 phosphorylation at serine-2814 increases cardiac tolerance to arrhythmogenic Ca2+ alternans in mice","volume":"200","author":"Valverde","year":"2025","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/S0021-9258(17)43484-3","article-title":"Phosphorylation-induced mobility shift in phospholamban in sodium dodecyl sulfate-polyacrylamide gels. Evidence for a protein structure consisting of multiple identical phosphorylatable subunits","volume":"259","author":"Wegener","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1016\/S0021-9258(19)41650-5","article-title":"Phosphorylation of a 22,000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3\u2032:5\u2032-monophosphate-dependent protein kinase","volume":"250","author":"Tada","year":"1975","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108118","DOI":"10.1016\/j.jbc.2024.108118","article-title":"Dilated cardiomyopathy variant R14del increases phospholamban pentamer stability, blunting dynamic regulation of calcium","volume":"301","author":"Cleary","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1161\/01.RES.0000258022.13090.55","article-title":"Ca2+\/calmodulin kinase II-dependent phosphorylation of ryanodine receptors suppresses Ca2+ sparks and Ca2+ waves in cardiac myocytes","volume":"100","author":"Yang","year":"2007","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nature02246","article-title":"The mitochondrial calcium uniporter is a highly selective ion channel","volume":"427","author":"Kirichok","year":"2004","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4949","DOI":"10.1021\/bi00234a016","article-title":"Inhibition of mitochondrial calcium ion transport by an oxo-bridged dinuclear ruthenium ammine complex","volume":"30","author":"Ying","year":"1991","journal-title":"Biochemistry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2025.04.008","article-title":"Mitochondrial calcium uniporter regulates human fibroblast-like synoviocytes invasion via altering mitochondrial dynamics and dictates rheumatoid arthritis pathogenesis","volume":"234","author":"Promila","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137514","DOI":"10.1016\/j.jhazmat.2025.137514","article-title":"Fluoride induces spermatocyte apoptosis by IP3R1\/MCU-mediated mitochondrial calcium overload through MAMs","volume":"489","author":"Guo","year":"2025","journal-title":"J. Hazard. Mater."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/181\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T05:17:44Z","timestamp":1769318264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["biom16020181"],"URL":"https:\/\/doi.org\/10.3390\/biom16020181","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}