{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:33:03Z","timestamp":1788208383015,"version":"build-2803163510"},"reference-count":118,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitochondrial dysfunctions are major contributors to heart disease onset and progression. Under ischemic injuries or cardiac overload, mitochondrial-derived oxidative stress, Ca2+ dis-homeostasis, and inflammation initiate cross-talking vicious cycles leading to defects of mitochondrial DNA, lipids, and proteins, concurrently resulting in fatal energy crisis and cell loss. Blunting such noxious stimuli and preserving mitochondrial homeostasis are essential to cell survival. In this context, mitochondrial quality control (MQC) represents an expanding research topic and therapeutic target in the field of cardiac physiology. MQC is a multi-tier surveillance system operating at the protein, organelle, and cell level to repair or eliminate damaged mitochondrial components and replace them by biogenesis. Novel evidence highlights the critical role of thyroid hormones (TH) in regulating multiple aspects of MQC, resulting in increased organelle turnover, improved mitochondrial bioenergetics, and the retention of cell function. In the present review, these emerging protective effects are discussed in the context of cardiac ischemia-reperfusion (IR) and heart failure, focusing on MQC as a strategy to blunt the propagation of connected dangerous signaling cascades and limit adverse remodeling. A better understanding of such TH-dependent signaling could provide insights into the development of mitochondria-targeted treatments in patients with cardiac disease.<\/jats:p>","DOI":"10.3390\/ijms20143377","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T11:56:51Z","timestamp":1562759811000},"page":"3377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Protective Effects of Euthyroidism Restoration on Mitochondria Function and Quality Control in Cardiac Pathophysiology"],"prefix":"10.3390","volume":"20","author":[{"given":"Francesca","family":"Forini","sequence":"first","affiliation":[{"name":"Institute of Clinical Physiology, CNR, via G.Moruzzi1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, CNR, via G.Moruzzi1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8064-8311","authenticated-orcid":false,"given":"Claudia","family":"Kusmic","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, CNR, via G.Moruzzi1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Iervasi","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology, CNR, via G.Moruzzi1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"H183","DOI":"10.1152\/ajpheart.00708.2014","article-title":"Mending a broken heart: The role of mitophagy in cardioprotection","volume":"308","author":"Moyzis","year":"2015","journal-title":"Am. J. Physiol. Heart. Circ. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1124\/pr.115.011502","article-title":"Mitochondrial Quality Control as a Therapeutic Target","volume":"68","author":"Suliman","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/cvr\/cvm005","article-title":"Heart mitochondria: Gates of life and death","volume":"77","author":"Gustafsson","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/403870","article-title":"Reactive Oxygen Species-Mediated Control of Mitochondrial Biogenesis","volume":"2012","author":"Yoboue","year":"2012","journal-title":"Int. J. Cell. Biol."},{"key":"ref_5","first-page":"1","article-title":"Role of ROS and RNS Sources in Physiological and Pathological Conditions","volume":"2016","author":"Reed","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ijcard.2013.12.014","article-title":"The breathing heart. Mitochondrial respiratory chain dysfunction in cardiac disease","volume":"171","author":"Schwarz","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1161\/01.RES.88.5.529","article-title":"Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction","volume":"88","author":"Ide","year":"2001","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s10741-016-9543-x","article-title":"Mitochondrial DNA repair: A novel therapeutic target for heart failure","volume":"21","year":"2016","journal-title":"Heart Fail. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1074\/jbc.M112.431973","article-title":"Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-\u03b2 Signaling","volume":"288","author":"Jain","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.redox.2015.09.009","article-title":"Reciprocal regulation of TGF-\u03b2 and reactive oxygen species A perverse cycle for fibrosis","volume":"6","author":"Liu","year":"2015","journal-title":"Redox Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.abb.2019.01.027","article-title":"Role of mitochondrial Ca2+ homeostasis in cardiac muscles","volume":"663","author":"Cao","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.mito.2013.01.003","article-title":"Mitochondrial dysfunction and the inflammatory response","volume":"13","year":"2013","journal-title":"Mitochondrion"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41419-017-0027-2","article-title":"Mitochondria-associated membranes (MAMs) and inflammation","volume":"9","author":"Missiroli","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3389\/fphys.2018.00755","article-title":"ER\u2013Mitochondria Microdomains in Cardiac Ischemia\u2013Reperfusion Injury: A Fresh Perspective","volume":"9","author":"Zhou","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26687","DOI":"10.3390\/ijms161125973","article-title":"Low T3 State Is Correlated with Cardiac Mitochondrial Impairments after Ischemia Reperfusion Injury: Evidence from a Proteomic Approach","volume":"16","author":"Forini","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13870","DOI":"10.1038\/s41598-018-32237-0","article-title":"Integrative analysis of differentially expressed genes and miRNAs predicts complex T3-mediated protective circuits in a rat model of cardiac ischemia reperfusion","volume":"8","author":"Forini","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1016\/j.jacc.2018.02.045","article-title":"Thyroid Hormones and Cardiovascular Function and Diseases","volume":"71","author":"Razvi","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1210\/er.2003-0033","article-title":"Thyroid Hormone Action in the Heart","volume":"26","author":"Kahali","year":"2005","journal-title":"Endocr. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1161\/01.CIR.0000048124.64204.3F","article-title":"Low-T3 syndrome: A strong prognostic predictor of death in patients with heart disease","volume":"107","author":"Iervasi","year":"2003","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1097\/PCC.0b013e3182917f87","article-title":"Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease","volume":"14","author":"Marwali","year":"2013","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.amjcard.2018.12.020","article-title":"Usefulness of Triiodothyronine Replacement Therapy in Patients With ST Elevation Myocardial Infarction and Borderline\/Reduced Triiodothyronine Levels","volume":"123","author":"Pingitore","year":"2019","journal-title":"Am. J. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10741-016-9545-8","article-title":"Cardioprotection and thyroid hormones","volume":"21","author":"Pingitore","year":"2016","journal-title":"Heart Fail. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3389\/fphys.2017.00225","article-title":"Modified Low-Dose Triiodo-L-thyronine Therapy Safely Improves Function Following Myocardial Ischemia-Reperfusion Injury","volume":"8","author":"Rajagopalan","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s00395-008-0697-0","article-title":"Long-term thyroid hormone administration re-shapes left ventricular chamber and improves cardiac function after myocardial infarction in rats","volume":"103","author":"Pantos","year":"2008","journal-title":"Basic. Res. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1139\/y2012-031","article-title":"Thyroid hormone and cardiac repair\/regeneration: From Prometheus myth to reality?","volume":"90","author":"Pantos","year":"2012","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1210\/jc.2007-2210","article-title":"Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: A randomized, placebo-controlled study","volume":"93","author":"Pingitore","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6312","DOI":"10.3390\/ijms16036312","article-title":"Mitochondria as key targets of cardioprotection in cardiac ischemic disease: Role of thyroid hormone triiodothyronine","volume":"16","author":"Forini","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1023\/B:MCBI.0000044321.17680.a2","article-title":"Bioenergetic remodeling of heart mitochondria by thyroid hormone","volume":"265","author":"Goldenthal","year":"2004","journal-title":"Mol. Cell. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1089\/thy.2007.0257","article-title":"Thyroid hormone regulation of heart metabolism","volume":"18","author":"Portman","year":"2008","journal-title":"Thyroid"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1582-4934.2010.01014.x","article-title":"Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac remodelling in rats","volume":"15","author":"Forini","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1210\/en.2014-1106","article-title":"Triiodothyronine prevents cardiac ischemia\/reperfusion mitochondrial impairment and cell loss by regulating miR30a\/p53 axis","volume":"155","author":"Forini","year":"2014","journal-title":"Endocrinology"},{"key":"ref_32","first-page":"263","article-title":"Early loss of cardiac function in acute myocardial infarction is associated with redox imbalance","volume":"17","author":"Tavares","year":"2012","journal-title":"Exp. Clin. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1161\/CIRCRESAHA.118.312708","article-title":"Mitochondrial ROS Drive Sudden Cardiac Death and Chronic Proteome Remodeling in Heart Failure","volume":"123","author":"Dey","year":"2018","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.mce.2014.04.010","article-title":"Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction","volume":"391","author":"Tavares","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11010-015-2501-4","article-title":"T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats","volume":"408","author":"Tavares","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.lfs.2015.12.052","article-title":"Thyroid hormones effects on oxidative stress and cardiac remodeling in the right ventricle of infarcted rats","volume":"146","author":"Corssac","year":"2016","journal-title":"Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.bbrc.2016.05.030","article-title":"3,3\u2032,5-triiodothyroxine inhibits apoptosis and oxidative stress by the PKM2\/PKM1 ratio during oxygen-glucose deprivation\/reperfusion AC16 and HCM-a cells: T3 inhibits apoptosis and oxidative stress by PKM2\/PKM1 ratioBiochem","volume":"17","author":"Li","year":"2016","journal-title":"Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.lfs.2015.07.026","article-title":"Molecular and biochemical evidences on the protective effects of triiodothyronine against phosphine-induced cardiac and mitochondrial toxicity","volume":"139","author":"Abdolghaffari","year":"2015","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11010-014-2292-z","article-title":"Modulation of apoptosis by sulforaphane is associated with PGC-1\u03b1 stimulation and decreased oxidative stress in cardiac myoblasts","volume":"401","author":"Fernandes","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1089\/ars.2009.2940","article-title":"PGC-1\u03b1 regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload","volume":"13","author":"Lu","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1159\/000374062","article-title":"MiR-31 downregulation protects against cardiac ischemia\/reperfusion injury by targeting protein kinase C epsilon (PKC\u03b5) directly","volume":"36","author":"Wang","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.yjmcc.2017.08.013","article-title":"MicroRNA-31 promotes adverse cardiac remodeling and dysfunction in ischemic heart disease","volume":"112","author":"Martinez","year":"2017","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1159\/000447853","article-title":"Cardiac-Specific Overexpression of miR-222 Induces Heart Failure and Inhibits Autophagy in Mice","volume":"39","author":"Su","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1161\/CIRCRESAHA.114.303784","article-title":"Loss of microRNA-155 Protects the Heart from Pathological Cardiac Hypertrophy","volume":"114","author":"Seok","year":"2014","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"H1295","DOI":"10.1152\/ajpheart.2001.281.3.H1295","article-title":"Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential","volume":"281","author":"Xu","year":"2001","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41580-018-0052-8","article-title":"The machineries, regulation and cellular functions of mitochondrial calcium","volume":"19","author":"Giorgi","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1074\/jbc.M610491200","article-title":"Ca2+ Activation kinetics of the two aspartate-glutamate mitochondrial carriers, aralar and citrin: Role in the heart malate-aspartate NADH shuttle","volume":"282","author":"Contreras","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1021\/bi052475e","article-title":"Mitochondrial matrix phosphoproteome: Effect of extra mitochondrial calcium","volume":"45","author":"Hopper","year":"2006","journal-title":"Biochemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/ncpcardio1301","article-title":"The cardiac sarcoplasmic\/endoplasmic reticulum calcium ATPase: A potent target for cardiovascular diseases","volume":"5","author":"Kawase","year":"2008","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.jacc.2007.12.014","article-title":"Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure","volume":"51","author":"Kawase","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"465","DOI":"10.2174\/1570161111311040010","article-title":"Benefit of SERCA2a gene transfer to vascular endothelial and smooth muscle cells: A new aspect in therapy of cardiovascular diseases","volume":"11","author":"Lipskaia","year":"2013","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1073\/pnas.97.2.793","article-title":"Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure","volume":"97","author":"Miyamoto","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.yjmcc.2009.08.031","article-title":"SERCA1 expression enhances the metabolic efficiency of improved contractility in post-ischemic heart","volume":"47","author":"Pound","year":"2009","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1006\/jmcc.1999.1095","article-title":"The Expression of SR Calcium Transport ATPase and the Na+\/Ca2+Exchanger are Antithetically Regulated During Mouse Cardiac Development and in Hypo\/hyperthyroidism","volume":"32","author":"Reed","year":"2000","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1161\/CIRCULATIONAHA.106.678326","article-title":"Thyroid Disease and the Heart","volume":"116","author":"Klein","year":"2007","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1161\/01.RES.75.2.245","article-title":"Thyroid hormone-induced alterations in phospholamban protein expression: Regulatory effects on sarcoplasmic reticulum Ca2 transport and myocardial relaxation","volume":"75","author":"Kiss","year":"1994","journal-title":"Circ Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0008-6363(01)00287-5","article-title":"3,5,3\u2032-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i of human cardiomyocytes in culture","volume":"51","author":"Forini","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1083\/jcb.201111095","article-title":"Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy","volume":"199","author":"Drawnel","year":"2012","journal-title":"J. Cell Boil."},{"key":"ref_59","first-page":"1375","article-title":"Type 3 inositol 1,4,5-trisphosphate receptor modulates cell death","volume":"14","author":"Blackshaw","year":"2000","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10750","DOI":"10.1074\/jbc.R112.420752","article-title":"The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Physiological Roles","volume":"288","author":"Patron","year":"2013","journal-title":"J. Boil. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.celrep.2015.06.002","article-title":"The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart","volume":"12","author":"Kwong","year":"2015","journal-title":"Cell Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijcard.2018.05.054","article-title":"Mitochondrial calcium uniporter inhibition provides cardioprotection in pressure overload-induced heart failure through autophagy enhancement","volume":"271","author":"Yu","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"E9006","DOI":"10.1073\/pnas.1708772114","article-title":"Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy","volume":"114","author":"Zaglia","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"900","DOI":"10.2119\/molmed.2015.00140","article-title":"Early and Short-term Triiodothyronine Supplementation Prevents Adverse Postischemic Cardiac Remodeling: Role of Transforming Growth Factor-\u03b21 and Antifibrotic miRNA Signaling","volume":"21","author":"Nicolini","year":"2016","journal-title":"Mol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nature07534","article-title":"Mitofusin 2 tethers endoplasmic reticulum to mitochondria","volume":"456","author":"Scorrano","year":"2008","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1161\/CIRCRESAHA.112.266585","article-title":"Mitofusin 2 containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca2+ crosstalk","volume":"111","author":"Chen","year":"2012","journal-title":"Circ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1172\/JCI120849","article-title":"Mitochondrial dysfunction in pathophysiology of heart failure","volume":"128","author":"Zhou","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.mce.2017.09.003","article-title":"Thyroid hormones decrease the proinflammatory TLR4\/NF-\u03ba\u03b2 pathway and improve functional parameters of the left ventricle of infarcted rats","volume":"461","author":"Fernandes","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.bbrc.2004.07.048","article-title":"Activation of nuclear factor-kappaB and its proinflammatory mediator cascade in the infarcted rat heart","volume":"321","author":"Lu","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"H530","DOI":"10.1152\/ajpheart.00549.2006","article-title":"Inhibition of NF-kappa B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction","volume":"292","author":"Onai","year":"2007","journal-title":"Am. J. Physiol. Heart. Circ. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Rajagopalan, V., Zhang, Y., Ojamaa, K., Chen, Y.F., Pingitore, A., Pol, C.J., Balasubramanian, K., Towner, R.A., and Gerdes, A.M. (2016). Safe oral triiodo-l-thyronine therapy protects from post-infarct cardiac dysfunction and arrhythmias without cardiovascular adverse effects. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151413"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neulet.2012.10.051","article-title":"BACE1 levels are elevated in congestive heart failure","volume":"532","author":"Mutlu","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jacc.2017.11.024","article-title":"Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction","volume":"71","author":"Thackeray","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1172\/JCI11205","article-title":"Protective responses in the ischemic myocardium. HSPs play an important role in the defense mechanism against IR injury","volume":"106","author":"Williams","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1161\/CIRCULATIONAHA.110.942250","article-title":"Hold me tight: The role of the HSP family of chaperones in cardiac disease","volume":"122","author":"Willis","year":"2010","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nrcardio.2017.89","article-title":"Proteostasis in cardiac health and disease","volume":"14","author":"Henning","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"H935","DOI":"10.1152\/ajpheart.00660.2001","article-title":"Increased expression of HSP27 protects canine myocytes from simulated ischemia reperfusion injury","volume":"282","author":"Heide","year":"2002","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1086\/302305","article-title":"Stress response proteins in cardiovascular disease","volume":"64","author":"Xiao","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.yjmcc.2006.06.068","article-title":"Heat shock protein upregulation protects against pacing-induced myolysis in HL-1 atrial myocytes and in human atrial fibrillation","volume":"41","author":"Brundel","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.tibs.2003.08.009","article-title":"More than folding: Localized functions of cytosolic chaperones","volume":"28","author":"Young","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tibs.2014.02.003","article-title":"FOXO transcription factors: Key regulators of cellular quality control","volume":"39","author":"Webb","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.yjmcc.2006.07.015","article-title":"Into the heart: The emerging role of the ubiquitin-proteasome system","volume":"41","author":"Willis","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1210\/en.2015-1632","article-title":"Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle","volume":"157","author":"Lesmana","year":"2016","journal-title":"Endocrinology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12929-019-0517-x","article-title":"Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases","volume":"26","author":"Chi","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lino, C.A., and Barreto-Chaves, M.L.M. (2012). Modulation of the ubiquitin proteasome system (UPS) in thyroid hormone-induced cardiac hypertrophy. FASEB J., 26.","DOI":"10.1096\/fasebj.26.1_supplement.1139.6"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Hauck, L., Stanley-Hasnain, S., Fung, A., Grothe, D., Rao, V., Mak, T.W., and Billia, F. (2017). Cardiac-specific ablation of the E3 ubiquitin ligase Mdm2 leads to oxidative stress, broad mitochondrial deficiency and early death. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189861"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e13003","DOI":"10.1111\/apha.13003","article-title":"Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation","volume":"222","author":"Ramos","year":"2018","journal-title":"Acta Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1016\/j.bbamcr.2013.07.015","article-title":"Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance","volume":"1833","author":"Kim","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fmicb.2018.00020","article-title":"MacroD1 Is a Promiscuous ADP-Ribosyl Hydrolase Localized to Mitochondria","volume":"9","author":"Agnew","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1126\/science.1106391","article-title":"Aconitase Couples Metabolic Regulation to Mitochondrial DNA Maintenance","volume":"307","author":"Chen","year":"2005","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6165","DOI":"10.1074\/jbc.M113.515130","article-title":"Mitochondria-targeted Ogg1 and Aconitase-2 Prevent Oxidant-induced Mitochondrial DNA Damage in Alveolar Epithelial Cells","volume":"289","author":"Kim","year":"2014","journal-title":"J. Boil. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nrcardio.2017.102","article-title":"New and revisited approaches to preserving the reperfused myocardium","volume":"14","author":"Kloner","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1161\/CIRCRESAHA.117.311082","article-title":"Autophagy and Mitophagy in Cardiovascular Disease","volume":"120","author":"Kroemer","year":"2017","journal-title":"Circ. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.116.303790","article-title":"The Molecular Mechanisms of Mitochondrial Autophagy Mitophagy in the heart","volume":"116","author":"Saito","year":"2015","journal-title":"Circ. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/15548627.2018.1511263","article-title":"Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy","volume":"15","author":"Yau","year":"2019","journal-title":"Autophagy"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1172\/JCI60580","article-title":"Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy","volume":"122","author":"Sinha","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1080\/15548627.2015.1061849","article-title":"Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling","volume":"11","author":"Sinha","year":"2015","journal-title":"Autophagy"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"eaam5855","DOI":"10.1126\/scisignal.aam5855","article-title":"Thyroid hormone receptor and ERR\u03b1 coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function","volume":"11","author":"Singh","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1038\/onc.2017.136","article-title":"Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover","volume":"36","author":"Chi","year":"2017","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.bbrc.2015.10.080","article-title":"Tri-iodothyronine preconditioning protects against liver ischemia reperfusion injury through the regulation of autophagy by the MEK ERK mTORC1 axis","volume":"467","author":"Yang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3389\/fphys.2019.00411","article-title":"Mitofusin 2 Participates in Mitophagy and Mitochondrial Fusion Against Angiotensin II-Induced Cardiomyocyte Injury","volume":"10","author":"Xiong","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00395-014-0423-z","article-title":"MicroRNA-144 is a circulating effector of remote ischemic preconditioning","volume":"109","author":"Li","year":"2014","journal-title":"Basic Res. Cardiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/cvr\/cvn098","article-title":"Transcriptional control of mitochondrial biogenesis: the central role of PGC-1","volume":"79","author":"Garnier","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10741-016-9561-8","article-title":"Mitochondrial pathways to cardiac recovery: TFAM","volume":"21","author":"Kunkel","year":"2016","journal-title":"Heart Fail. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1677\/jme.0.0260067","article-title":"Thyroid hormone action in mitochondria","volume":"26","author":"Casas","year":"2001","journal-title":"J. Mol. Endocrinol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.yjmcc.2005.03.016","article-title":"Nuclear-mitochondrial cross-talk in cardiomyocyte T3 signaling: A time-course analysis","volume":"39","author":"Goldenthal","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.vph.2009.10.008","article-title":"Thyroid hormone and myocardial mitochondrial biogenesis","volume":"52","year":"2010","journal-title":"Vascul Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2011.05.009","article-title":"Coordination of mitochondrial biogenesis by thyroid hormone","volume":"342","author":"Weitzel","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.mce.2008.01.017","article-title":"T3-mediated expression of PGC-1\u03b1 via a far upstream located thyroid hormone response element","volume":"287","author":"Wulf","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/348137a0","article-title":"Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins","volume":"348","author":"Kang","year":"1990","journal-title":"Nature"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"E29","DOI":"10.1152\/ajpendo.00294.2002","article-title":"Functional consequences of thyroid hormone-induced changes in the mitochondrial protein import pathway","volume":"284","author":"Colavecchia","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"C1508","DOI":"10.1152\/ajpcell.1998.275.6.C1508","article-title":"Thyroid hormone modifies mitochondrial phenotype by increasing protein import without altering degradation","volume":"275","author":"Craig","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1677\/joe.0.1650009","article-title":"Effect of thyroid hormone on mthsp70 expression, mitochondrial import, and processing in cardiac muscle","volume":"165","author":"Schneider","year":"2000","journal-title":"J. Endocrinol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1006\/bbrc.2000.3589","article-title":"Functional analysis of human metaxin in mitochondrial protein import in cultured cells and its relationship with the Tom complex","volume":"276","author":"Abdul","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1093\/emboj\/19.23.6392","article-title":"The role of the TIM8\u201313 complex in the import of Tim23 into mitochondria","volume":"19","author":"Paschen","year":"2000","journal-title":"EMBO J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1210\/me.2013-1414","article-title":"Deciphering direct and indirect influence of thyroid hormone with mouse genetics","volume":"4","author":"Picou","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1161\/CIRCHEARTFAILURE.108.810747","article-title":"Physiological Replacement of T 3 Improves Left Ventricular Function in an Animal Model of Myocardial Infarction-Induced Congestive Heart Failure","volume":"2","author":"Henderson","year":"2009","journal-title":"Circ. Heart Fail."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1530\/EJE-11-0062","article-title":"Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: A strong association?","volume":"165","author":"Lymvaios","year":"2011","journal-title":"Eur. J. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/14\/3377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:04:05Z","timestamp":1760187845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/14\/3377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,10]]},"references-count":118,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["ijms20143377"],"URL":"https:\/\/doi.org\/10.3390\/ijms20143377","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,10]]}}}