{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:52:51Z","timestamp":1785433971852,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19 CDA 34660311"],"award-info":[{"award-number":["19 CDA 34660311"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"award":["19 CDA 34660311"],"award-info":[{"award-number":["19 CDA 34660311"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIH","doi-asserted-by":"publisher","award":["R35GM151226"],"award-info":[{"award-number":["R35GM151226"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIH","doi-asserted-by":"publisher","award":["R35GM151096"],"award-info":[{"award-number":["R35GM151096"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIH","doi-asserted-by":"publisher","award":["P01 AG001751"],"award-info":[{"award-number":["P01 AG001751"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R35GM151226"],"award-info":[{"award-number":["R35GM151226"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35GM151096"],"award-info":[{"award-number":["R35GM151096"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P01 AG001751"],"award-info":[{"award-number":["P01 AG001751"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NSF","award":["2217757"],"award-info":[{"award-number":["2217757"]}]},{"award":["2217757"],"award-info":[{"award-number":["2217757"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Doxorubicin (DOX), an effective chemotherapeutic agent for many types of cancer, is known for significant cardiotoxic side effects, which largely limit its clinical usage. A 3 h treatment of cardiomyoblast H9C2 cells with a low concentration of DOX (100 nM) can induce senescence-associated \u03b2-galactosidase (SA \u03b2-gal) staining, a gold standard of cell senescence. In the current study, we comprehensively characterized the phenotype of the DOX-induced senescent cardiomyocytes for the first time. Establishing this in vitro model will facilitate an expanded capacity for searching for effective treatments for DOX-induced cell senescence. Using SA \u03b2-gal staining and cell growth rate as readouts, we assessed the concentration-dependent effect of DOX on H9C2 cell senescence. The cells were treated with DOX for 3 h and subsequently cultured for 3 days. We found that a 50 nM concentration of DOX induced ~50% SA \u03b2-gal staining and completely inhibited cell growth. The DOX-induced H9C2 cell senescence was further confirmed by several well-accepted senescence markers, including cell hypertrophy, increased p16 and p21 expression, increased Senescence Associated Secretory Phenotype (SASP) markers, arrested cell cycle, and increased ROS production. Interestingly, we found that 50 nM DOX increased mitochondrial respiration. Translationally, we found that mitochondrial-targeted tetrapeptide SS-31 (elamipretide, 1 \u00b5M) partially attenuated 50 nM DOX-induced SA \u03b2-gal staining from 51.4% to 35.8%. SS-31 also prevented increases in the p16, p21, and SASP markers and mitigated mitochondrial ROS production. Additionally, SS-31 reversed the 50 nM DOX-induced elevation of mitochondrial respiration. However, 1 \u00b5M SS-31 failed to prevent the cell cycle arrest induced by 50 nM DOX. Using a 3 h treatment of 50 nM DOX, we established an H9C2 cell senescence model. Treatment with SS-31 attenuates this DOX-induced cell senescence but not the cell cycle arrest. These data suggest that SS-31 is a promising drug to treat DOX-induced cardiomyocyte senescence.<\/jats:p>","DOI":"10.3390\/biology15131034","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence"],"prefix":"10.3390","volume":"15","author":[{"given":"Jiaojiao","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics & Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, 3440 N Broad St., Kresge Hall, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9682-0910","authenticated-orcid":false,"given":"Shuo","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics & Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, 3440 N Broad St., Kresge Hall, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3366-5805","authenticated-orcid":false,"given":"Songlin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics & Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, 3440 N Broad St., Kresge Hall, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific St., Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1261-1362","authenticated-orcid":false,"given":"Xingyun","family":"Qi","sequence":"additional","affiliation":[{"name":"JHSC Building, Department of Biology, Rutgers University, Camden, NJ 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-1219","authenticated-orcid":false,"given":"Huiliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics & Molecular Biochemistry, Lewis Katz School of Medicine, Temple University, 3440 N Broad St., Kresge Hall, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1200\/JCO.2011.39.9014","article-title":"Cardiopulmonary function and age-related decline across the breast cancer survivorship continuum","volume":"30","author":"Jones","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cardinale, D., Iacopo, F., and Cipolla, C.M. (2020). Cardiotoxicity of Anthracyclines. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00026"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schirone, L., D\u2019Ambrosio, L., Forte, M., Genovese, R., Schiavon, S., Spinosa, G., Iacovone, G., Valenti, V., Frati, G., and Sciarretta, S. (2022). Mitochondria and Doxorubicin-Induced Cardiomyopathy: A Complex Interplay. Cells, 11.","DOI":"10.3390\/cells11132000"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41514-024-00135-7","article-title":"A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging","volume":"10","author":"Linders","year":"2024","journal-title":"npj Aging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nrm3823","article-title":"Cellular senescence: From physiology to pathology","volume":"15","author":"Serrano","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1172\/JCI95146","article-title":"Senescent cells: A therapeutic target for cardiovascular disease","volume":"128","author":"Childs","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jjcc.2019.05.002","article-title":"Cellular senescence in cardiac diseases","volume":"74","author":"Shimizu","year":"2019","journal-title":"J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41420-023-01792-5","article-title":"Cardiac cell senescence: Molecular mechanisms, key proteins and therapeutic targets","volume":"10","author":"Luan","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1038\/s41598-018-37862-3","article-title":"Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration","volume":"9","author":"Abdullah","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106356","DOI":"10.1016\/j.phrs.2022.106356","article-title":"Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice","volume":"183","author":"Alfonso","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13788","DOI":"10.18632\/aging.202972","article-title":"Redd1 knockdown prevents doxorubicin-induced cardiac senescence","volume":"13","author":"Huang","year":"2021","journal-title":"Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1474-9726.2007.00358.x","article-title":"Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage","volume":"7","author":"Maejima","year":"2008","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"H2169","DOI":"10.1152\/ajpheart.00068.2009","article-title":"Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2","volume":"297","author":"Spallarossa","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Altieri, P., Spallarossa, P., Barisione, C., Garibaldi, S., Garuti, A., Fabbi, P., Ghigliotti, G., and Brunelli, C. (2012). Inhibition of doxorubicin-induced senescence by PPARdelta activation agonists in cardiac muscle cells: Cooperation between PPARdelta and Bcl6. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046126"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"148949","DOI":"10.1016\/j.bbabio.2022.148949","article-title":"Inner mitochondrial membrane structure and fusion dynamics are altered in senescent human iPSC-derived and primary rat cardiomyocytes","volume":"1864","author":"Morris","year":"2023","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e70388","DOI":"10.1111\/acel.70388","article-title":"Disruption of ATP Synthase Spatiotemporal Organization, Ca2+ Dynamics, and Contractile Function in Senescent Cardiomyocytes","volume":"25","author":"Morris","year":"2026","journal-title":"Aging Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jaccao.2023.03.012","article-title":"Evaluation of Senescence and Its Prevention in Doxorubicin-Induced Cardiotoxicity Using Dynamic Engineered Heart Tissues","volume":"5","author":"Linders","year":"2023","journal-title":"JACC CardioOncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C380","DOI":"10.1152\/ajpcell.00073.2019","article-title":"Accelerated cardiomyocyte senescence contributes to late-onset doxorubicin-induced cardiotoxicity","volume":"318","author":"Mitry","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Suda, M., Paul, K.H., Minamino, T., Miller, J.D., Lerman, A., Ellison-Hughes, G.M., Tchkonia, T., and Kirkland, J.L. (2023). Senescent Cells: A Therapeutic Target in Cardiovascular Diseases. Cells, 12.","DOI":"10.3390\/cells12091296"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1681\/ASN.2012121216","article-title":"The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin","volume":"24","author":"Birk","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/clpt.2014.174","article-title":"Serendipity and the discovery of novel compounds that restore mitochondrial plasticity","volume":"96","author":"Szeto","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1111\/bph.12461","article-title":"First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics","volume":"171","author":"Szeto","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e002206","DOI":"10.1161\/CIRCHEARTFAILURE.115.002206","article-title":"Chronic Therapy with Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs with Advanced Heart Failure","volume":"9","author":"Sabbah","year":"2016","journal-title":"Circ. Heart Fail."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6662156","DOI":"10.1155\/2021\/6662156","article-title":"SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization","volume":"2021","author":"Shang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Escribano-Lopez, I., de Maranon, A.M., Iannantuoni, F., Lopez-Domenech, S., Abad-Jimenez, Z., Diaz, P., Sola, E., Apostolova, N., Rocha, M., and Victor, V.M. (2019). The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes. J. Clin. Med., 8.","DOI":"10.3390\/jcm8091322"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12974-019-1627-9","article-title":"Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice","volume":"16","author":"Zhao","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1113\/jphysiol.2014.286518","article-title":"Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy","volume":"593","author":"Min","year":"2015","journal-title":"J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R227","DOI":"10.1152\/ajpregu.00299.2019","article-title":"Doxorubicin-induced oxidative stress differentially regulates proteolytic signaling in cardiac and skeletal muscle","volume":"318","author":"Montalvo","year":"2020","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e60827","DOI":"10.7554\/eLife.60827","article-title":"Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte","volume":"9","author":"Zhang","year":"2020","journal-title":"eLife"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e55513","DOI":"10.7554\/eLife.55513","article-title":"Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice","volume":"9","author":"Chiao","year":"2020","journal-title":"eLife"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3892\/ijmm.2021.4896","article-title":"Peptide Szeto-Schiller 31 ameliorates doxorubicin-induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway","volume":"47","author":"Zhang","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wen, J., Zhang, L., Liu, H., Wang, J., Li, J., Yang, Y., Wang, Y., Cai, H., Li, R., and Zhao, Y. (2019). Salsolinol Attenuates Doxorubicin-Induced Chronic Heart Failure in Rats and Improves Mitochondrial Function in H9c2 Cardiomyocytes. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01135"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1093\/cvr\/cvw212","article-title":"A novel fission-independent role of dynamin-related protein 1 in cardiac mitochondrial respiration","volume":"113","author":"Zhang","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/febs.15570","article-title":"A guide to assessing cellular senescence in vitro and in vivo","volume":"288","author":"Baker","year":"2021","journal-title":"FEBS J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1600-079X.2012.01003.x","article-title":"Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction","volume":"53","author":"Song","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1111\/bph.12468","article-title":"Targeting mitochondrial cardiolipin and the cytochrome c\/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis","volume":"171","author":"Birk","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S453","DOI":"10.3233\/JAD-220514","article-title":"The Novel Role of Mitochondrial Citrate Synthase and Citrate in the Pathophysiology of Alzheimer\u2019s Disease","volume":"94","author":"Chhimpa","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_38","first-page":"186","article-title":"Honokiol antagonizes doxorubicin-induced cardiomyocyte senescence by inhibiting TXNIP-mediated NLRP3 inflammasome activation","volume":"45","author":"Huang","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Foglio, E., D\u2019Avorio, E., Vitiello, L., Masuelli, L., Bei, R., Pacifici, F., Della-Morte, D., Mirabilii, S., Ricciardi, M.R., and Tafuri, A. (2023). Doxorubicin-Induced Cardiac Senescence Is Alleviated Following Treatment with Combined Polyphenols and Micronutrients through Enhancement in Mitophagy. Cells, 12.","DOI":"10.3390\/cells12222605"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e002383","DOI":"10.1161\/JAHA.115.002383","article-title":"Testosterone Antagonizes Doxorubicin-Induced Senescence of Cardiomyocytes","volume":"5","author":"Altieri","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1179\/135100007X162112","article-title":"Bioenergetics in aging: Mitochondrial proton leak in aging rat liver, kidney and heart","volume":"12","author":"Serviddio","year":"2007","journal-title":"Redox Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ejca.2005.11.003","article-title":"Caring for survivors of childhood cancers: The size of the problem","volume":"42","author":"Curry","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3565127","DOI":"10.1155\/2016\/3565127","article-title":"ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases","volume":"2016","author":"Davalli","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/cvr\/cvt050","article-title":"ROS regulation of microdomain Ca2+ signalling at the dyads","volume":"98","author":"Zhang","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/bs.ircmb.2018.05.006","article-title":"Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases","volume":"340","author":"Giorgi","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1007\/s11357-023-00757-x","article-title":"Mitochondrial proton leak in cardiac aging","volume":"45","author":"Qi","year":"2023","journal-title":"GeroScience"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1167\/iovs.15-17758","article-title":"PGC-1alpha Induces Human RPE Oxidative Metabolism and Antioxidant Capacity","volume":"57","author":"Iacovelli","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1242\/jcs.113662","article-title":"PGC1alpha and mitochondrial metabolism\u2013emerging concepts and relevance in ageing and neurodegenerative disorders","volume":"125","author":"Austin","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s12012-020-09576-4","article-title":"Involvement of ROS\/NLRP3 Inflammasome Signaling Pathway in Doxorubicin-Induced Cardiotoxicity","volume":"20","author":"Wei","year":"2020","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110525","DOI":"10.1016\/j.biopha.2020.110525","article-title":"NF-kappaB pathway activation during endothelial-to-mesenchymal transition in a rat model of doxorubicin-induced cardiotoxicity","volume":"130","author":"Xu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"116337","DOI":"10.1016\/j.biopha.2024.116337","article-title":"The Janus face of mitophagy in myocardial ischemia\/reperfusion injury and recovery","volume":"173","author":"Deng","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.yjmcc.2018.08.022","article-title":"Heart specific knockout of Ndufs4 ameliorates ischemia reperfusion injury","volume":"123","author":"Zhang","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, M., Zhu, Z., He, X., Dai, S., Liu, R., and Liu, J. (2025). The crosstalk between mitochondrial dysfunction and fatty acid metabolism in heart failure: Mechanisms and therapeutic strategies. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1679085"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/13\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:45:43Z","timestamp":1782967543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/13\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":54,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["biology15131034"],"URL":"https:\/\/doi.org\/10.3390\/biology15131034","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]}}}