{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:00:54Z","timestamp":1792036854419,"version":"4.4.0"},"reference-count":243,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["GSO\/EKFS 14"],"award-info":[{"award-number":["GSO\/EKFS 14"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heart failure remains the most common cause of death in the industrialized world. In spite of new therapeutic interventions that are constantly being developed, it is still not possible to completely protect against heart failure development and progression. This shows how much more research is necessary to understand the underlying mechanisms of this process. In this review, we give a detailed overview of the contribution of impaired mitochondrial dynamics and energy homeostasis during heart failure progression. In particular, we focus on the regulation of fatty acid metabolism and the effects of fatty acid accumulation on mitochondrial structural and functional homeostasis.<\/jats:p>","DOI":"10.3390\/ijms22031498","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T13:01:12Z","timestamp":1612270872000},"page":"1498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mitochondrial Homeostasis Mediates Lipotoxicity in the Failing Myocardium"],"prefix":"10.3390","volume":"22","author":[{"given":"Tom","family":"Kretzschmar","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena, 07747 Jena, Th\u00fcringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine M. F.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena, 07747 Jena, Th\u00fcringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Christian","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Jena, 07747 Jena, Th\u00fcringen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Inamdar, A.A., and Inamdar, A.C. (2016). Heart Failure: Diagnosis, Management and Utilization. J. Clin. Med., 5.","DOI":"10.3390\/jcm5070062"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1161\/CIRCULATIONAHA.117.031841","article-title":"Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy","volume":"137","author":"Scally","year":"2018","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.cjca.2017.03.009","article-title":"Complex Energy Metabolic Changes in Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction","volume":"33","author":"Lopaschuk","year":"2017","journal-title":"Can. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jpba.2018.03.027","article-title":"LC-MS-based serum fingerprinting reveals significant dysregulation of phospholipids in chronic heart failure","volume":"154","author":"Ciborowski","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15420\/cfr.2018.27.2","article-title":"Biomarkers in Routine Heart Failure Clinical Care","volume":"5","author":"Nadar","year":"2019","journal-title":"Card. Fail. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.hfc.2017.08.011","article-title":"Metabolic Biomarkers in Heart Failure","volume":"14","author":"Albert","year":"2018","journal-title":"Heart Fail. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lund, A., Nordrehaug, J.E., Slettom, G., Solvang, S.H., Pedersen, E.K., Midttun, O., Ulvik, A., Ueland, P.M., Nygard, O., and Giil, L.M. (2020). Plasma kynurenines and prognosis in patients with heart failure. PloS ONE, 15.","DOI":"10.1371\/journal.pone.0230056"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"64793","DOI":"10.18632\/oncotarget.18334","article-title":"Spermine and spermidine reversed age-related cardiac deterioration in rats","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_10","unstructured":"Hage, C., Lofgren, L., Michopoulos, F., Nilsson, R., Davidsson, P., Kumar, C., Ekstrom, M., Eriksson, M.J., Lynga, P., and Persson, B. (2020). Metabolomic Profile in Patients with Heart Failure With Preserved Ejection Fraction Versus Patients With Heart Failure With Reduced Ejection Fraction. J. Card. Fail."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Haase, D., Baz, L., Bekfani, T., Neugebauer, S., Kiehntopf, M., Mobius-Winkler, S., Franz, M., and Schulze, P.C. (2020). Metabolomic profiling of patients with high gradient aortic stenosis undergoing transcatheter aortic valve replacement. Clin. Res. Cardiol.","DOI":"10.1007\/s00392-020-01754-2"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11897-013-0133-0","article-title":"Cardiac lipotoxicity: Molecular pathways and therapeutic implications","volume":"10","author":"Drosatos","year":"2013","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1161\/CIRCRESAHA.116.306842","article-title":"Lipid Use and Misuse by the Heart","volume":"118","author":"Schulze","year":"2016","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3389\/fcell.2019.00042","article-title":"Fatty Acid Oxidation Promotes Cardiomyocyte Proliferation Rate but Does Not Change Cardiomyocyte Number in Infant Mice","volume":"7","author":"Cao","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Horikoshi, Y., Yan, Y., Terashvili, M., Wells, C., Horikoshi, H., Fujita, S., Bosnjak, Z.J., and Bai, X. (2019). Fatty Acid-Treated Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes Exhibit Adult Cardiomyocyte-Like Energy Metabolism Phenotypes. Cells, 8.","DOI":"10.3390\/cells8091095"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00395-020-0796-0","article-title":"Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells","volume":"115","author":"Bekhite","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"ref_17","first-page":"H1698","article-title":"Glycolysis is predominant source of myocardial ATP production immediately after birth","volume":"261","author":"Lopaschuk","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1161\/01.RES.0000064382.46274.95","article-title":"PPARs of the heart: Three is a crowd","volume":"92","author":"Kelly","year":"2003","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kalliora, C., Kyriazis, I.D., Oka, S.I., Lieu, M.J., Yue, Y., Area-Gomez, E., Pol, C.J., Tian, Y., Mizushima, W., and Chin, A. (2019). Dual peroxisome-proliferator-activated-receptor-alpha\/gamma activation inhibits SIRT1-PGC1alpha axis and causes cardiac dysfunction. JCI Insight, 5.","DOI":"10.1172\/jci.insight.129556"},{"key":"ref_20","first-page":"1007","article-title":"PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation","volume":"1812","author":"Varga","year":"2011","journal-title":"B.B.A."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.semcdb.2012.01.003","article-title":"PPARs: Fatty acid sensors controlling metabolism","volume":"23","author":"Poulsen","year":"2012","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"835985","DOI":"10.1155\/2015\/835985","article-title":"PPARs: Protectors or Opponents of Myocardial Function?","volume":"2015","author":"Pol","year":"2015","journal-title":"PPAR Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mce.2010.05.019","article-title":"Peroxisome proliferator activated receptor alpha (PPARalpha) and PPAR gamma coactivator (PGC-1alpha) induce carnitine palmitoyltransferase IA (CPT-1A) via independent gene elements","volume":"325","author":"Song","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15703","DOI":"10.1074\/jbc.M110158200","article-title":"Dual promoter structure of mouse and human fatty acid translocase\/CD36 genes and unique transcriptional activation by peroxisome proliferator-activated receptor alpha and gamma ligands","volume":"277","author":"Sato","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1152\/physrev.00015.2009","article-title":"Myocardial fatty acid metabolism in health and disease","volume":"90","author":"Lopaschuk","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"22293","DOI":"10.1074\/jbc.M000248200","article-title":"Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity","volume":"275","author":"Watanabe","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1161\/CIRCULATIONAHA.105.534594","article-title":"Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilization","volume":"112","author":"Luptak","year":"2005","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bse0470001","article-title":"The mitochondrial respiratory chain","volume":"47","author":"Rich","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.semcdb.2017.07.021","article-title":"Respiratory chain supercomplexes: Structures, function and biogenesis","volume":"76","author":"Ugalde","year":"2018","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nrm3997","article-title":"A giant molecular proton pump: Structure and mechanism of respiratory complex I","volume":"16","author":"Sazanov","year":"2015","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.semcdb.2017.08.011","article-title":"Building a complex complex: Assembly of mitochondrial respiratory chain complex I","volume":"76","author":"Formosa","year":"2018","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1146\/annurev.biochem.72.121801.161700","article-title":"Function and structure of complex II of the respiratory chain","volume":"72","author":"Cecchini","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"ref_33","first-page":"1320","article-title":"Superoxide generation by complex III: From mechanistic rationales to functional consequences","volume":"1827","author":"Bleier","year":"2013","journal-title":"B.B.A."},{"key":"ref_34","first-page":"436","article-title":"Respiratory chain proteins","volume":"147","author":"Kadenbach","year":"1991","journal-title":"Rev. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"291","DOI":"10.15252\/embj.201695021","article-title":"Complex structure of cytochrome c-cytochrome c oxidase reveals a novel protein-protein interaction mode","volume":"36","author":"Shimada","year":"2017","journal-title":"EMBO J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1042\/BST20160139","article-title":"Mitochondrial cytochrome c oxidase: Catalysis, coupling and controversies","volume":"45","author":"Rich","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10545-011-9382-9","article-title":"Mitochondrial ATP synthase: Architecture, function and pathology","volume":"35","author":"Jonckheere","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/bmc-2019-0001","article-title":"ATP Synthase: Structure, Function and Inhibition","volume":"10","author":"Neupane","year":"2019","journal-title":"Biomol. Concepts"},{"key":"ref_39","first-page":"9","article-title":"Cardiological manifestations of mitochondrial respiratory chain disorders","volume":"30","author":"Berardo","year":"2011","journal-title":"Acta Myol."},{"key":"ref_40","first-page":"1368","article-title":"Mitochondrial respiratory chain disorders in childhood: Insights into diagnosis and management in the new era of genomic medicine","volume":"1840","author":"Menezes","year":"2014","journal-title":"B.B.A"},{"key":"ref_41","unstructured":"Shemesh, A., and Margolin, E. (2020). Kearns Sayre Syndrome. StatPearls, StatPearls Publishing."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/17474086.2018.1426454","article-title":"Pearson syndrome","volume":"11","author":"Farruggia","year":"2018","journal-title":"Expert. Rev. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s002469900084","article-title":"Cardiac mitochondrial dysfunction in Leigh syndrome","volume":"17","author":"Ananthakrishnan","year":"1996","journal-title":"Pediatr. Cardiol."},{"key":"ref_44","first-page":"965","article-title":"Tissue specificity of mitochondrial glutamate pathways and the control of metabolic homeostasis","volume":"1777","author":"Frigerio","year":"2008","journal-title":"B.B.A."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12079-015-0315-5","article-title":"A pathway map of glutamate metabolism","volume":"10","author":"Yelamanchi","year":"2016","journal-title":"J. Cell. Commun. Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/0305-0491(93)90031-Y","article-title":"L-glutamate dehydrogenases: Distribution, properties and mechanism","volume":"106","author":"Hudson","year":"1993","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/mrdd.1040","article-title":"Disorders of glutamate metabolism","volume":"7","author":"Kelly","year":"2001","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1126\/science.6121377","article-title":"Abnormal glutamate metabolism in an adult-onset degenerative neurological disorder","volume":"216","author":"Plaitakis","year":"1982","journal-title":"Science"},{"key":"ref_49","first-page":"528940","article-title":"Abnormalities in glutamate metabolism and excitotoxicity in the retinal diseases","volume":"2013","author":"Ishikawa","year":"2013","journal-title":"Scientifica (Cairo)"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S1095-6433(03)00007-2","article-title":"Glycolysis and pyruvate oxidation in cardiac hypertrophy--why so unbalanced?","volume":"135","author":"Leong","year":"2003","journal-title":"Comp. Biochem. Physiol. A. Mol. Integr. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1042\/BST20120041","article-title":"Allosteric regulation of the biotin-dependent enzyme pyruvate carboxylase by acetyl-CoA","volume":"40","author":"Zeczycki","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1007\/s00018-013-1539-2","article-title":"Regulation of pyruvate metabolism and human disease","volume":"71","author":"Gray","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.cell.2018.08.040","article-title":"Acetate Production from Glucose and Coupling to Mitochondrial Metabolism in Mammals","volume":"175","author":"Liu","year":"2018","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/ajh.25325","article-title":"Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency","volume":"94","author":"Bianchi","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-physiol-021115-105045","article-title":"The Biochemistry and Physiology of Mitochondrial Fatty Acid beta-Oxidation and Its Genetic Disorders","volume":"78","author":"Houten","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A general introduction to the biochemistry of mitochondrial fatty acid beta-oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14501","DOI":"10.1074\/jbc.275.19.14501","article-title":"Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase","volume":"275","author":"Bonen","year":"2000","journal-title":"J. Biol.Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s11745-003-1089-6","article-title":"Long-chain fatty acid uptake by skeletal muscle is impaired in homozygous, but not heterozygous, heart-type-FABP null mice","volume":"38","author":"Luiken","year":"2003","journal-title":"Lipids"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16522","DOI":"10.1074\/jbc.M109.004788","article-title":"Greater transport efficiencies of the membrane fatty acid transporters FAT\/CD36 and FATP4 compared with FABPpm and FATP1 and differential effects on fatty acid esterification and oxidation in rat skeletal muscle","volume":"284","author":"Nickerson","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"31717","DOI":"10.1074\/jbc.M400100200","article-title":"Structural basis of the substrate-specific two-step catalysis of long chain fatty acyl-CoA synthetase dimer","volume":"279","author":"Hisanaga","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cmet.2010.05.012","article-title":"Adipose acyl-CoA synthetase-1 directs fatty acids toward beta-oxidation and is required for cold thermogenesis","volume":"12","author":"Ellis","year":"2010","journal-title":"Cell Met."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1161\/CIRCULATIONAHA.119.039610","article-title":"Preservation of Acyl Coenzyme A Attenuates Pathological and Metabolic Cardiac Remodeling Through Selective Lipid Trafficking","volume":"139","author":"Goldenberg","year":"2019","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.mad.2012.01.007","article-title":"Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart","volume":"133","author":"Gomez","year":"2012","journal-title":"Mech. Ageing Dev."},{"key":"ref_64","first-page":"2422","article-title":"Carnitine transport and fatty acid oxidation","volume":"1863","author":"Longo","year":"2016","journal-title":"B.B.A."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/humu.20085","article-title":"Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency","volume":"24","author":"Iacobazzi","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lehmann, D., Motlagh, L., Robaa, D., and Zierz, S. (2017). Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010082"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jocn.2018.11.023","article-title":"Phenotype of carnitine palmitoyltransferase II (CPT II) deficiency: A questionnaire-based survey","volume":"59","author":"Joshi","year":"2019","journal-title":"J. Clin. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1074\/jbc.RA119.011526","article-title":"Targeting viperin to the mitochondrion inhibits the thiolase activity of the trifunctional enzyme complex","volume":"295","author":"Dumbrepatil","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1107\/S1399004714023827","article-title":"The crystal structure of human mitochondrial 3-ketoacyl-CoA thiolase (T1): insight into the reaction mechanism of its thiolase and thioesterase activities","volume":"70","author":"Kiema","year":"2014","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Martines, A.M.F., van Eunen, K., Reijngoud, D.J., and Bakker, B.M. (2017). The promiscuous enzyme medium-chain 3-keto-acyl-CoA thiolase triggers a vicious cycle in fatty-acid beta-oxidation. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005461"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"158813","DOI":"10.1016\/j.bbalip.2020.158813","article-title":"Ketone metabolism in the failing heart","volume":"1865","author":"Lopaschuk","year":"2020","journal-title":"B.B.A. Mol. Cell. Biol. Lipids"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Du, Z., Shen, A., Huang, Y., Su, L., Lai, W., Wang, P., Xie, Z., Xie, Z., Zeng, Q., and Ren, H. (2014). 1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients. PloS ONE, 9.","DOI":"10.1371\/journal.pone.0088102"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1161\/CIRCULATIONAHA.115.017545","article-title":"Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure","volume":"133","author":"Bedi","year":"2016","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/CIRCULATIONAHA.115.017355","article-title":"The Failing Heart Relies on Ketone Bodies as a Fuel","volume":"133","author":"Aubert","year":"2016","journal-title":"Circulation"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbrc.2016.05.097","article-title":"beta-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes","volume":"475","author":"Nagao","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ho, K.L., Karwi, Q.G., Wagg, C., Zhang, L., Vo, K., Altamimi, T., Uddin, G.M., Ussher, J.R., and Lopaschuk, G.D. (2020). Ketones can become the major fuel source for the heart but do not increase cardiac efficiency. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvaa143"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1093\/cvr\/cvz045","article-title":"Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency","volume":"115","author":"Ho","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/s42255-020-00288-1","article-title":"Mitochondrial pyruvate carriers are required for myocardial stress adaptation","volume":"2","author":"Zhang","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/s42255-020-00276-5","article-title":"Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy","volume":"2","author":"Kamynina","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/s42255-020-00296-1","article-title":"Nutritional modulation of heart failure in mitochondrial pyruvate carrier-deficient mice","volume":"2","author":"McCommis","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1172\/JCI10947","article-title":"A novel mouse model of lipotoxic cardiomyopathy","volume":"107","author":"Chiu","year":"2001","journal-title":"J. Clin. Invest."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12933-017-0528-4","article-title":"Regulation of visceral and epicardial adipose tissue for preventing cardiovascular injuries associated to obesity and diabetes","volume":"16","author":"Gonzalez","year":"2017","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20","DOI":"10.14797\/mdcj-13-1-20","article-title":"Epicardial Fat in the Maintenance of Cardiovascular Health","volume":"13","author":"Wu","year":"2017","journal-title":"Methodist Debakey Cardiovasc. J."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Song, Y., Song, F., Wu, C., Hong, Y.X., and Li, G. (2020). The roles of epicardial adipose tissue in heart failure. Heart failure reviews.","DOI":"10.1007\/s10741-020-09997-x"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1007\/s00125-012-2598-x","article-title":"Adiponectin: Mechanistic insights and clinical implications","volume":"55","author":"Turer","year":"2012","journal-title":"Diabetologia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.pharmthera.2004.08.012","article-title":"Adrenomedullin: Regulator of systemic and cardiac homeostasis in acute myocardial infarction","volume":"105","author":"Hamid","year":"2005","journal-title":"Pharmacol. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.cardfail.2015.07.014","article-title":"Altered Levels of Fatty Acids and Inflammatory and Metabolic Mediators in Epicardial Adipose Tissue in Patients With Systolic Heart Failure","volume":"21","author":"Fosshaug","year":"2015","journal-title":"J. Card. Fail."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"14","DOI":"10.15420\/ecr.2018:10:2","article-title":"Familial Hypercholesterolaemia Diagnosis and Management","volume":"13","author":"Alonso","year":"2018","journal-title":"Eur. Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/nhs.12218","article-title":"Lifestyle habits and obesity progression in overweight and obese American young adults: Lessons for promoting cardiometabolic health","volume":"17","author":"Cha","year":"2015","journal-title":"Nurs. Health Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.2174\/138920012803762729","article-title":"Fatty acids - induced lipotoxicity and inflammation","volume":"13","author":"Savary","year":"2012","journal-title":"Curr. Drug Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.3389\/fphys.2018.01866","article-title":"Cardiolipotoxicity, Inflammation, and Arrhythmias: Role for Interleukin-6 Molecular Mechanisms","volume":"9","author":"Ali","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1194\/jlr.M800147-JLR200","article-title":"Ceramide is a cardiotoxin in lipotoxic cardiomyopathy","volume":"49","author":"Park","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/iub.319","article-title":"Mammalian ceramide synthases","volume":"62","author":"Levy","year":"2010","journal-title":"IUBMB life"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1042\/BJ20111626","article-title":"Ceramide synthases at the centre of sphingolipid metabolism and biology","volume":"441","author":"Mullen","year":"2012","journal-title":"Biochem. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"33931","DOI":"10.1074\/jbc.M608092200","article-title":"Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity","volume":"281","author":"Spassieva","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"43452","DOI":"10.1074\/jbc.M307104200","article-title":"Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors","volume":"278","author":"Riebeling","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1042\/BJ20050291","article-title":"Mammalian Lass6 and its related family members regulate synthesis of specific ceramides","volume":"390","author":"Mizutani","year":"2005","journal-title":"Biochem. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1042\/BJ20060379","article-title":"LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity","volume":"398","author":"Mizutani","year":"2006","journal-title":"Biochem. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1194\/jlr.M800158-JLR200","article-title":"2-Hydroxy-ceramide synthesis by ceramide synthase family: Enzymatic basis for the preference of FA chain length","volume":"49","author":"Mizutani","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"27366","DOI":"10.1074\/jbc.M703487200","article-title":"A new functional motif in Hox domain-containing ceramide synthases: Identification of a novel region flanking the Hox and TLC domains essential for activity","volume":"282","author":"Mesika","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1042\/BJ20060697","article-title":"Transmembrane topology of ceramide synthase in yeast","volume":"398","author":"Riezman","year":"2006","journal-title":"Biochem. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.cellsig.2007.12.006","article-title":"The sphingolipid salvage pathway in ceramide metabolism and signaling","volume":"20","author":"Kitatani","year":"2008","journal-title":"Cell. Signal."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"22137","DOI":"10.1016\/S0021-9258(18)45681-5","article-title":"A temperature-sensitive mammalian cell mutant with thermolabile serine palmitoyltransferase for the sphingolipid biosynthesis","volume":"265","author":"Hanada","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_104","first-page":"1474","article-title":"Mechanistic enzymology of serine palmitoyltransferase","volume":"1814","author":"Ikushiro","year":"2011","journal-title":"B.B.A."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"18429","DOI":"10.1074\/jbc.M111.296947","article-title":"Cardiomyocyte specific deficiency of serine palmitoyltransferase subunit 2 reduces ceramide but leads to cardiac dysfunction","volume":"287","author":"Lee","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ji, R., Akashi, H., Drosatos, K., Liao, X., Jiang, H., Kennel, P.J., Brunjes, D.L., Castillero, E., Zhang, X., and Deng, L.Y. (2017). Increased de novo ceramide synthesis and accumulation in failing myocardium. JCI insight, 2.","DOI":"10.1172\/jci.insight.82922"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Campisi, G.M., Signorelli, P., Rizzo, J., Ghilardi, C., Antognetti, J., Caretti, A., Lazarevic, J.S., Strettoi, E., Novelli, E., and Ghidoni, R. (2017). Determination of the serine palmitoyl transferase inhibitor myriocin by electrospray and Q-trap mass spectrometry. Biomed. Chromatogr., 31.","DOI":"10.1002\/bmc.4026"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00395-016-0533-x","article-title":"Inhibition of ceramide de novo synthesis as a postischemic strategy to reduce myocardial reperfusion injury","volume":"111","author":"Reforgiato","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"986","DOI":"10.3389\/fphys.2019.00986","article-title":"Sphingolipid Synthesis Inhibition by Myriocin Administration Enhances Lipid Consumption and Ameliorates Lipid Response to Myocardial Ischemia Reperfusion Injury","volume":"10","author":"Bonezzi","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1073\/pnas.88.10.4250","article-title":"Expression of growth\/differentiation factor 1 in the nervous system: Conservation of a bicistronic structure","volume":"88","author":"Lee","year":"1991","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"35642","DOI":"10.1074\/jbc.M205211200","article-title":"Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells","volume":"277","author":"Venkataraman","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_112","first-page":"905","article-title":"LASS6, an additional member of the longevity assurance gene family","volume":"16","author":"Weinmann","year":"2005","journal-title":"Int. J. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1074\/jbc.M707386200","article-title":"Characterization of ceramide synthase 2: Tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate","volume":"283","author":"Laviad","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Wang, J.Y., Yan, W., Wang, D.D., Yang, S.J., Zhou, S.Y., Zhong, S.L., and Tang, J.H. (2019). Clinical and pathological significance of Homo sapiens ceramide synthase 2 (CerS-2) in diverse human cancers. Biosci. Rep., 39.","DOI":"10.1042\/BSR20181743"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1096\/fj.201700300R","article-title":"Lipotoxic very-long-chain ceramides cause mitochondrial dysfunction, oxidative stress, and cell death in cardiomyocytes","volume":"32","author":"Law","year":"2018","journal-title":"FASEB Journal."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1172\/JCI63888","article-title":"Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes","volume":"122","author":"Russo","year":"2012","journal-title":"J. Clin. Invest."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.molmet.2018.12.008","article-title":"The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach","volume":"21","author":"Raichur","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/j.cell.2019.05.008","article-title":"CerS6-Derived Sphingolipids Interact with Mff and Promote Mitochondrial Fragmentation in Obesity","volume":"177","author":"Hammerschmidt","year":"2019","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1093\/hmg\/ddr494","article-title":"Loss of ceramide synthase 3 causes lethal skin barrier disruption","volume":"21","author":"Jennemann","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/jdv.13777","article-title":"Ceramide synthase 4 is highly expressed in involved skin of patients with atopic dermatitis","volume":"31","author":"Ito","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"104022","DOI":"10.18632\/oncotarget.21955","article-title":"Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nchembio.1059","article-title":"Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy","volume":"8","author":"Sentelle","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"258","DOI":"10.4161\/auto.22739","article-title":"Ceramide stress in survival versus lethal autophagy paradox: Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy","volume":"9","author":"Jiang","year":"2013","journal-title":"Autophagy"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e13049","DOI":"10.1111\/acel.13049","article-title":"A tissue-specific screen of ceramide expression in aged mice identifies ceramide synthase-1 and ceramide synthase-5 as potential regulators of fiber size and strength in skeletal muscle","volume":"19","author":"Tosetti","year":"2020","journal-title":"Aging Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fcell.2016.00085","article-title":"The Evolution of Per-cell Organelle Number","volume":"4","author":"Cole","year":"2016","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1242\/jcs.114.5.867","article-title":"Control of mitochondrial morphology by a human mitofusin","volume":"114","author":"Santel","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41419-017-0023-6","article-title":"Mitofusin 2: From functions to disease","volume":"9","author":"Filadi","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phrs.2018.01.003","article-title":"Highlighting the endoplasmic reticulum-mitochondria connection: Focus on Mitofusin 2","volume":"128","author":"Filadi","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1042\/EBC20170104","article-title":"Mitochondrial dynamics: Overview of molecular mechanisms","volume":"62","author":"Tilokani","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development","volume":"160","author":"Chen","year":"2003","journal-title":"J Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"H167","DOI":"10.1152\/ajpheart.00833.2011","article-title":"Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death","volume":"302","author":"Papanicolaou","year":"2012","journal-title":"Am. J. Physiol. Heart Circ."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1128\/MCB.00774-13","article-title":"Mitofusin 1 is negatively regulated by microRNA 140 in cardiomyocyte apoptosis","volume":"34","author":"Li","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41467-018-08276-6","article-title":"A selective inhibitor of mitofusin 1-betaIIPKC association improves heart failure outcome in rats","volume":"10","author":"Ferreira","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1161\/CIRCRESAHA.111.258723","article-title":"Mitochondrial fusion is essential for organelle function and cardiac homeostasis","volume":"109","author":"Chen","year":"2011","journal-title":"Circ. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1128\/MCB.00911-10","article-title":"Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes","volume":"31","author":"Papanicolaou","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e2238","DOI":"10.1038\/cddis.2016.139","article-title":"Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction","volume":"7","author":"Hall","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.7150\/thno.33684","article-title":"Targeting mitochondrial dynamics by regulating Mfn2 for therapeutic intervention in diabetic cardiomyopathy","volume":"9","author":"Hu","year":"2019","journal-title":"Theranostics"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ceca.2014.11.002","article-title":"Role of Mitofusin-2 in mitochondrial localization and calcium uptake in skeletal muscle","volume":"57","author":"Ainbinder","year":"2015","journal-title":"Cell Calcium"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1242\/jcs.159186","article-title":"OPA1 processing in cell death and disease - the long and short of it","volume":"129","author":"MacVicar","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Lee, H., and Yoon, Y. (2018). Mitochondrial Membrane Dynamics-Functional Positioning of OPA1. Antioxidants, 7.","DOI":"10.3390\/antiox7120186"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/jmedgenet-2015-103361","article-title":"Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation","volume":"53","author":"Spiegel","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/nrm3013","article-title":"Mitochondrial fusion and fission in cell life and death","volume":"11","author":"Westermann","year":"2010","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1042\/BST20160129","article-title":"Mitochondrial fission and fusion","volume":"44","author":"Lee","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/embor.2011.54","article-title":"MiD49 and MiD51, new components of the mitochondrial fission machinery","volume":"12","author":"Palmer","year":"2011","journal-title":"EMBO Rep."},{"key":"ref_145","first-page":"239","article-title":"MiD49 and MiD51: New mediators of mitochondrial fission and novel targets for cardioprotection","volume":"1","author":"Samangouei","year":"2018","journal-title":"Cond. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"27584","DOI":"10.1074\/jbc.M113.479873","article-title":"Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission","volume":"288","author":"Palmer","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1242\/jcs.185165","article-title":"Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission","volume":"129","author":"Osellame","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.tibs.2015.09.002","article-title":"Dynamics-Driven Allostery in Protein Kinases","volume":"40","author":"Kornev","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41586-018-0211-2","article-title":"Structural basis of mitochondrial receptor binding and constriction by DRP1","volume":"558","author":"Kalia","year":"2018","journal-title":"Nature"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e13204","DOI":"10.1111\/eci.13204","article-title":"The impact of DRP1 on myocardial fibrosis in the obese minipig","volume":"50","author":"Chen","year":"2020","journal-title":"Eur J. Clin. Investig."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/iub.71","article-title":"Shaping mitochondria: The complex posttranslational regulation of the mitochondrial fission protein DRP1","volume":"60","author":"Santel","year":"2008","journal-title":"IUBMB life"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.molcel.2015.01.002","article-title":"Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth","volume":"57","author":"Kashatus","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1091\/mbc.e16-04-0208","article-title":"Novel regulatory roles of Mff and Drp1 in E3 ubiquitin ligase MARCH5-dependent degradation of MiD49 and Mcl1 and control of mitochondrial dynamics","volume":"28","author":"Cherok","year":"2017","journal-title":"Mol. Biol. Cell."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1096\/fj.09-136630","article-title":"SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle","volume":"23","author":"Stadler","year":"2009","journal-title":"FASEB J."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.molcel.2019.01.036","article-title":"Probing the Global Cellular Responses to Lipotoxicity Caused by Saturated Fatty Acids","volume":"74","author":"Piccolis","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1083\/jcb.201007152","article-title":"Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells","volume":"191","author":"Otera","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1242\/jcs.01058","article-title":"Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology","volume":"117","author":"Stojanovski","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_158","first-page":"860","article-title":"High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy","volume":"1777","author":"Gomes","year":"2008","journal-title":"B.B.A."},{"key":"ref_159","first-page":"150","article-title":"Recent advances into the understanding of mitochondrial fission","volume":"1833","author":"Elgass","year":"2013","journal-title":"B.B.A."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.molcel.2016.02.022","article-title":"Mitofusins, from Mitochondria to Metabolism","volume":"61","author":"Schrepfer","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Zhao, N., Zhang, Y., Liu, Q., and Xiang, W. (2015). Mfn2 Affects Embryo Development via Mitochondrial Dysfunction and Apoptosis. PloS ONE, 10.","DOI":"10.1371\/journal.pone.0125680"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1073\/pnas.1108220109","article-title":"Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis","volume":"109","author":"Sebastian","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1093\/hmg\/ddi149","article-title":"The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system","volume":"14","author":"Pich","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"17190","DOI":"10.1074\/jbc.M212754200","article-title":"Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity","volume":"278","author":"Bach","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1089\/ars.2014.6208","article-title":"Mitofusin 2 as a driver that controls energy metabolism and insulin signaling","volume":"22","author":"Zorzano","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"733","DOI":"10.3389\/fphys.2019.00733","article-title":"Mitofusin 2 Is Essential for IP3-Mediated SR\/Mitochondria Metabolic Feedback in Ventricular Myocytes","volume":"10","author":"Seidlmayer","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1161\/CIRCRESAHA.116.303356","article-title":"Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress","volume":"116","author":"Ikeda","year":"2015","journal-title":"Circ. Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.15252\/embj.201488658","article-title":"Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain","volume":"33","author":"Kageyama","year":"2014","journal-title":"EMBO J."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cmet.2014.12.011","article-title":"Mitochondrial fission and fusion factors reciprocally orchestrate mitophagic culling in mouse hearts and cultured fibroblasts","volume":"21","author":"Song","year":"2015","journal-title":"Cell Met."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1161\/CIRCULATIONAHA.109.906610","article-title":"Inhibiting mitochondrial fission protects the heart against ischemia\/reperfusion injury","volume":"121","author":"Ong","year":"2010","journal-title":"Circulation"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"e000461","DOI":"10.1161\/JAHA.113.000461","article-title":"Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction","volume":"2","author":"Disatnik","year":"2013","journal-title":"J. Am. Heart Assoc."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.yjmcc.2019.04.006","article-title":"Drp1\/Fis1 interaction mediates mitochondrial dysfunction in septic cardiomyopathy","volume":"130","author":"Haileselassie","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1161\/CIRCRESAHA.119.315252","article-title":"Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction","volume":"126","author":"Hu","year":"2020","journal-title":"Circ. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tem.2015.12.001","article-title":"Mitochondrial Dynamics and Metabolic Regulation","volume":"27","author":"Wai","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0196-0644(87)80059-8","article-title":"Verapamil reverses calcium cardiotoxicity","volume":"16","author":"Zaloga","year":"1987","journal-title":"Ann. Emerg. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/978-94-007-2888-2_52","article-title":"Remodeling of calcium handling in human heart failure","volume":"740","author":"Lou","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cmet.2015.01.005","article-title":"Altered myocardial calcium cycling and energetics in heart failure\u2014A rational approach for disease treatment","volume":"21","author":"Gorski","year":"2015","journal-title":"Cell Met."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Samuel, T.J., Rosenberry, R.P., Lee, S., and Pan, Z. (2018). Correcting Calcium Dysregulation in Chronic Heart Failure Using SERCA2a Gene Therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041086"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.amjmed.2018.10.006","article-title":"The Association Between Serum Calcium Levels and Short-Term Mortality in Patients with Chronic Heart Failure","volume":"132","author":"Jensen","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1161\/01.CIR.0000068316.53218.49","article-title":"Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure","volume":"107","author":"Reiken","year":"2003","journal-title":"Circulation"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/ejcts\/ezy139","article-title":"Management of hypercalcaemia-induced heart failure using mechanical circulatory support","volume":"54","author":"Knoll","year":"2018","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1161\/CIRCRESAHA.114.300568","article-title":"Role of RyR2 phosphorylation in heart failure and arrhythmias: Controversies around ryanodine receptor phosphorylation in cardiac disease","volume":"114","author":"Dobrev","year":"2014","journal-title":"Circ. Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"11389","DOI":"10.1073\/pnas.1513047112","article-title":"Mitochondrial calcium overload is a key determinant in heart failure","volume":"112","author":"Santulli","year":"2015","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1517\/14712590903321462","article-title":"Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure","volume":"10","author":"Lipskaia","year":"2010","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"237","DOI":"10.5483\/BMBRep.2013.46.5.077","article-title":"SERCA2a: A prime target for modulation of cardiac contractility during heart failure","volume":"46","author":"Park","year":"2013","journal-title":"BMB Rep."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ceca.2007.11.014","article-title":"The cellular concentration of Bcl-2 determines its pro- or anti-apoptotic effect","volume":"44","author":"Hanson","year":"2008","journal-title":"Cell Calcium"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/ncb894","article-title":"Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits apoptosis","volume":"5","author":"Shirane","year":"2003","journal-title":"Nat. Cell. Biol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"40493","DOI":"10.1074\/jbc.M606181200","article-title":"Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression","volume":"281","author":"Portier","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Riley, J.S., Quarato, G., Cloix, C., Lopez, J., O\u2019Prey, J., Pearson, M., Chapman, J., Sesaki, H., Carlin, L.M., and Passos, J.F. (2018). Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis. EMBO J., 37.","DOI":"10.15252\/embj.201899238"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s11064-011-0457-7","article-title":"Inositol 1,4,5-trisphosphate receptor subtype-specific regulation of calcium oscillations","volume":"36","author":"Zhang","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ceca.2007.11.015","article-title":"High- and low-calcium-dependent mechanisms of mitochondrial calcium signalling","volume":"44","author":"Spat","year":"2008","journal-title":"Cell Calcium"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"e00704","DOI":"10.7554\/eLife.00704","article-title":"MCU encodes the pore conducting mitochondrial calcium currents","volume":"2","author":"Chaudhuri","year":"2013","journal-title":"Elife"},{"key":"ref_193","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_194","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.mito.2009.02.005","article-title":"Mitofusin-2 regulates mitochondrial and endoplasmic reticulum morphology and tethering: The role of Ras","volume":"9","author":"Scorrano","year":"2009","journal-title":"Mitochondrion"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"40892","DOI":"10.1074\/jbc.M506623200","article-title":"The type III inositol 1,4,5-trisphosphate receptor preferentially transmits apoptotic Ca2+ signals into mitochondria","volume":"280","author":"Mendes","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s00395-020-00835-7","article-title":"Reduced reticulum-mitochondria Ca(2+) transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy","volume":"115","author":"Dia","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"13678","DOI":"10.1074\/jbc.M109.096040","article-title":"Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling","volume":"285","author":"Eckenrode","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"19414","DOI":"10.1074\/jbc.M101590200","article-title":"Bcl-xL promotes the open configuration of the voltage-dependent anion channel and metabolite passage through the outer mitochondrial membrane","volume":"276","author":"Li","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"5454","DOI":"10.1128\/MCB.20.15.5454-5468.2000","article-title":"BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore","volume":"20","author":"Cizeau","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1096\/fj.08-124354","article-title":"BNIP3 mediates cell death by different pathways following localization to endoplasmic reticulum and mitochondrion","volume":"23","author":"Zhang","year":"2009","journal-title":"FASEB J."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.molmet.2014.05.004","article-title":"ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload","volume":"3","author":"Egnatchik","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1042\/BJ20070319","article-title":"Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak","volume":"405","author":"Kubli","year":"2007","journal-title":"Biochem. J."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/embor.2010.50","article-title":"The BH3-only Bnip3 binds to the dynamin Opa1 to promote mitochondrial fragmentation and apoptosis by distinct mechanisms","volume":"11","author":"Landes","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00246-010-9876-5","article-title":"Bnip3 as a dual regulator of mitochondrial turnover and cell death in the myocardium","volume":"32","author":"Gustafsson","year":"2011","journal-title":"Pediatr. Cardiol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1161\/01.RES.0000029232.42227.16","article-title":"Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes","volume":"91","author":"Regula","year":"2002","journal-title":"Circ. Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/sj.cdd.4401936","article-title":"Response to myocardial ischemia\/reperfusion injury involves Bnip3 and autophagy","volume":"14","author":"Brady","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cca.2020.02.024","article-title":"Bnip3 in mitophagy: Novel insights and potential therapeutic target for diseases of secondary mitochondrial dysfunction","volume":"506","author":"Gao","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-physiol-021317-121427","article-title":"The Role of Autophagy in the Heart","volume":"80","author":"Sciarretta","year":"2018","journal-title":"Ann. Rev. Physiol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"419","DOI":"10.14336\/AD.2019.0518","article-title":"Role of Mitophagy in Cardiovascular Disease","volume":"11","author":"Yang","year":"2020","journal-title":"Aging Dis."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Chi, C., Riching, A.S., and Song, K. (2020). Lysosomal Abnormalities in Cardiovascular Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030811"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"297","DOI":"10.4161\/auto.18658","article-title":"Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death","volume":"8","author":"Ma","year":"2012","journal-title":"Autophagy"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"H2025","DOI":"10.1152\/ajpheart.00552.2008","article-title":"Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemia and reperfusion","volume":"295","author":"Kubli","year":"2008","journal-title":"Am. J. Physiol. Heart Circ."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.15252\/embj.201593084","article-title":"Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway","volume":"35","author":"Sebastian","year":"2016","journal-title":"EMBO J."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Li, P.L., and Zhang, Y. (2013). Cross talk between ceramide and redox signaling: Implications for endothelial dysfunction and renal disease. Handb. Exp. Pharmacol.","DOI":"10.1007\/978-3-7091-1511-4_9"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1089\/ars.2017.7467","article-title":"Bioactive Lipids and Redox Signaling: Molecular Mechanism and Disease Pathogenesis","volume":"28","author":"Li","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1756-8722-6-19","article-title":"Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers","volume":"6","author":"Li","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1134\/S0006297915050028","article-title":"Mitochondrial ROS Metabolism: 10 Years Later","volume":"80","author":"Andreyev","year":"2015","journal-title":"Biochemistry (Mosc)"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"8516","DOI":"10.1074\/jbc.M210432200","article-title":"Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production","volume":"278","author":"Li","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mito.2019.07.003","article-title":"Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling","volume":"49","author":"Wu","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Joseph, L.C., Kokkinaki, D., Valenti, M.C., Kim, G.J., Barca, E., Tomar, D., Hoffman, N.E., Subramanyam, P., Colecraft, H.M., and Hirano, M. (2017). Inhibition of NADPH oxidase 2 (NOX2) prevents sepsis-induced cardiomyopathy by improving calcium handling and mitochondrial function. JCI insight, 2.","DOI":"10.1172\/jci.insight.94248"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1161\/CIRCHEARTFAILURE.111.961565","article-title":"p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation","volume":"5","author":"Nakamura","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1161\/CIRCRESAHA.117.311307","article-title":"Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial Fission","volume":"122","author":"Tsushima","year":"2018","journal-title":"Circ. Res."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1007\/s00125-010-1684-1","article-title":"Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: The missing links. The Claude Bernard Lecture 2009","volume":"53","author":"DeFronzo","year":"2010","journal-title":"Diabetologia"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s11906-012-0307-2","article-title":"Mechanisms of lipotoxicity in the cardiovascular system","volume":"14","author":"Wende","year":"2012","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-3-319-48382-5_12","article-title":"Insulin Resistance, Obesity and Lipotoxicity","volume":"960","author":"Yazici","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"H778","DOI":"10.1152\/ajpheart.00749.2019","article-title":"PKCdelta causes sepsis-induced cardiomyopathy by inducing mitochondrial dysfunction","volume":"318","author":"Joseph","year":"2020","journal-title":"Am. J. Physiol. Heart Circ."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1161\/01.CIR.0000101682.24138.36","article-title":"Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo","volume":"108","author":"Inagaki","year":"2003","journal-title":"Circulation"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.abb.2005.05.007","article-title":"Translocation of deltaPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function","volume":"439","author":"Churchill","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"47985","DOI":"10.1074\/jbc.M405071200","article-title":"Protein kinase Cdelta activation induces apoptosis in response to cardiac ischemia and reperfusion damage: A mechanism involving BAD and the mitochondria","volume":"279","author":"Murriel","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1007\/s00018-012-0925-5","article-title":"SIRT1 modulates MAPK pathways in ischemic-reperfused cardiomyocytes","volume":"69","author":"Becatti","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1161\/CIRCRESAHA.110.227371","article-title":"Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes","volume":"107","author":"Hariharan","year":"2010","journal-title":"Circ. Res."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.2337\/db12-0533","article-title":"Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes","volume":"62","author":"He","year":"2013","journal-title":"Diabetes"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"H1558","DOI":"10.1152\/ajpheart.00865.2013","article-title":"Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial dysfunction in type 2 diabetic hearts: Potential role of NO\/SIRT1\/PGC-1alpha signaling","volume":"306","author":"Koka","year":"2014","journal-title":"Am. J. Physiol. Heart Circ."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"14447","DOI":"10.1073\/pnas.0803790105","article-title":"A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis","volume":"105","author":"Ahn","year":"2008","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1161\/CIRCULATIONAHA.117.030486","article-title":"MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in Sirtuin 3 Expression and Mitochondrial Protein Acetylation","volume":"137","author":"Zhang","year":"2018","journal-title":"Circulation"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Chen, T., Liu, J., Li, N., Wang, S., Liu, H., Li, J., Zhang, Y., and Bu, P. (2015). Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD. PloS ONE, 10.","DOI":"10.1371\/journal.pone.0118909"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s00395-015-0493-6","article-title":"SIRT3 deficiency impairs mitochondrial and contractile function in the heart","volume":"110","author":"Koentges","year":"2015","journal-title":"Basic Res. Cardiol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1172\/JCI79964","article-title":"Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis","volume":"125","author":"Liao","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1161\/CIRCRESAHA.115.306383","article-title":"Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function","volume":"118","author":"Drosatos","year":"2016","journal-title":"Circ. Res."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.1074\/jbc.M113.531384","article-title":"Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism","volume":"289","author":"Prosdocimo","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Sato, P.Y., Chuprun, J.K., Grisanti, L.A., Woodall, M.C., Brown, B.R., Roy, R., Traynham, C.J., Ibetti, J., Lucchese, A.M., and Yuan, A. (2018). Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation. Sci. Signal., 11.","DOI":"10.1126\/scisignal.aau0144"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.yjmcc.2015.10.002","article-title":"GRK2 compromises cardiomyocyte mitochondrial function by diminishing fatty acid-mediated oxygen consumption and increasing superoxide levels","volume":"89","author":"Sato","year":"2015","journal-title":"J. Mol. Cell. Cardiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:19:06Z","timestamp":1760159946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":243,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031498"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031498","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]}}}