{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T09:04:18Z","timestamp":1779699858202,"version":"3.53.1"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Thoracic Surgery Foundation Resident Research Fellowship Award"},{"name":"Merit Review Grants","award":["1I01 BX003859"],"award-info":[{"award-number":["1I01 BX003859"]}]},{"name":"Merit Review Grants","award":["2I01 BX001355"],"award-info":[{"award-number":["2I01 BX001355"]}]},{"name":"Pauley Heart Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Donation after circulatory death (DCD) involves unavoidable ischemia\u2013reperfusion injury (IRI). Mitochondrial permeability transition pore (MPTP) opening plays a critical role in DCD heart injury. Activation of ubiquitous calpains, including calpain-1 and calpain-2 (CPN1\/2), increases MPTP opening in DCD hearts. Mitofilin, a mitochondrial inner membrane protein that regulates cristae morphology, is also involved in MPTP opening during ischemia\u2013reperfusion. However, it remains unclear whether CPN1\/2 activation contributes to mitofilin-mediated IRI in DCD hearts. We first incubated a mitofilin peptide with exogenous CPN1 in vitro to investigate the link between CPN1 activation and mitofilin degradation. Next, we tested whether CPN1\/2 inhibition reduces cardiac injury in DCD hearts by preserving mitofilin and limiting MPTP opening. Sprague-Dawley (SD) rat hearts were subjected to 25 min of in vivo ischemia followed by ex vivo perfusion with or without the CPN1\/2 inhibitor MDL-28170 (10 \u00b5M). In vitro incubation with CPN1 led to mitofilin degradation, confirming mitofilin as a CPN1 substrate. CPN1\/2 inhibition significantly reduced infarct size compared with untreated DCD hearts, preserved mitofilin expression, and decreased MPTP opening. These findings indicate that CPN1\/2 activation promotes MPTP opening in DCD hearts through mitofilin degradation. Timely inhibition of CPN1\/2 represents a promising strategy to reduce cardiac injury and improve DCD heart function.<\/jats:p>","DOI":"10.3390\/cells15100920","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitofilin Preservation Mitigates Cardiac Injury in Donation-After-Circulatory-Death Hearts"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5683-7844","authenticated-orcid":false,"given":"Qun","family":"Chen","sequence":"first","affiliation":[{"name":"Departments of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6126-4766","authenticated-orcid":false,"given":"Zachary","family":"Kiernan","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Labate","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-2323","authenticated-orcid":false,"given":"Oluwatoyin","family":"Akande","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Lesnefsky","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Department of Cellular, Molecular and Genetic Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Richmond Department of Veterans Affairs Medical Center, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-043X","authenticated-orcid":false,"given":"Mohammed","family":"Quader","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Virginia Commonwealth University, Richmond, VA 23298, USA"},{"name":"Richmond Department of Veterans Affairs Medical Center, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100917","DOI":"10.1016\/j.trre.2025.100917","article-title":"Survival after heart transplants from circulatory-dead versus brain-dead donors: Meta-analysis of reconstructed time-to-event data","volume":"39","author":"Wang","year":"2025","journal-title":"Transplant. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Resch, T., Cardini, B., Oberhuber, R., Weissenbacher, A., Dumfarth, J., Krapf, C., Boesmueller, C., Oefner, D., Grimm, M., and Schneeberger, S. (2020). Transplanting Marginal Organs in the Era of Modern Machine Perfusion and Advanced Organ Monitoring. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00631"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1007\/s11886-022-01798-y","article-title":"Donation After Circulatory Death: A New Frontier","volume":"24","author":"Joshi","year":"2022","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kenny, L.A., Armstrong, L., Berman, M., Brierley, J., Crossland, D., Dark, J., Gardiner, D., Large, S.R., Manas, D., and Nassar, M. (2025). Heart Transplantation and Donation After Circulatory Death in Children. A Review of the Technological, Logistical and Ethical Framework. Transpl. Int., 38.","DOI":"10.3389\/ti.2025.13801"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1016\/j.jtcvs.2023.09.012","article-title":"Donation after circulatory death improves probability of heart transplantation in waitlisted candidates and results in post-transplant outcomes similar to those achieved with brain-dead donors","volume":"167","author":"Hess","year":"2024","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/j.ajt.2025.01.019","article-title":"OPTN\/SRTR 2023 Annual Data Report: Introduction","volume":"25","author":"Schladt","year":"2025","journal-title":"Am. J. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Quader, M., Akande, O., Toldo, S., Cholyway, R., Kang, L., Lesnefsky, E.J., and Chen, Q. (2020). The Commonalities and Differences in Mitochondrial Dysfunction Between ex vivo and in vivo Myocardial Global Ischemia Rat Heart Models: Implications for Donation After Circulatory Death Research. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00681"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.jacc.2023.08.006","article-title":"Outcomes of Heart Transplant Donation After Circulatory Death","volume":"82","author":"Siddiqi","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1265","DOI":"10.1097\/TXD.0000000000001265","article-title":"Mitochondrial Damage-associated Molecular Patterns as Potential Biomarkers in DCD Heart Transplantation: Lessons From Myocardial Infarction and Cardiac Arrest","volume":"8","author":"Longnus","year":"2022","journal-title":"Transplant. Direct"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31236","DOI":"10.1038\/s41598-024-82578-2","article-title":"Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death","volume":"14","author":"Doulamis","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1186\/s12967-025-06805-8","article-title":"Exploring mitochondrial health and transplantation strategies in DCD heart transplantation: A systematic review","volume":"23","author":"Zhang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lewis, M.J., Khaliulin, I., Hall, K., and Suleiman, M.S. (2022). Cardioprotection of Immature Heart by Simultaneous Activation of PKA and Epac: A Role for the Mitochondrial Permeability Transition Pore. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202201.0116.v1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e011846","DOI":"10.1161\/CIRCHEARTFAILURE.124.011846","article-title":"Infarct Size Reduction With Cyclosporine A in Circulatory Death Rat Hearts: Reducing Effective Ischemia Time With Therapy During Reperfusion","volume":"17","author":"Kiernan","year":"2024","journal-title":"Circ. Heart Fail."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1113\/jphysiol.2003.034231","article-title":"Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart","volume":"549","author":"Javadov","year":"2003","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ejphar.2008.12.024","article-title":"Mechanism for resveratrol-induced cardioprotection against reperfusion injury involves glycogen synthase kinase 3beta and mitochondrial permeability transition pore","volume":"604","author":"Xi","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1161\/RES.0000000000000104","article-title":"Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association","volume":"118","author":"Murphy","year":"2016","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/FJC.0000000000001290","article-title":"Modulation of Mitochondrial Respiration During Early Reperfusion Reduces Cardiac Injury in Donation After Circulatory Death Hearts","volume":"80","author":"Akande","year":"2022","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C28","DOI":"10.1152\/ajpcell.00230.2017","article-title":"Mitochondrial inner membrane protein (mitofilin) knockdown induces cell death by apoptosis via an AIF-PARP-dependent mechanism and cell cycle arrest","volume":"315","author":"Madungwe","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.freeradbiomed.2020.06.039","article-title":"Cardiac ischemia\/reperfusion stress reduces inner mitochondrial membrane protein (mitofilin) levels during early reperfusion","volume":"158","author":"Tombo","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Feng, Y., Imam Aliagan, A., Tombo, N., and Bopassa, J.C. (2023). Mitofilin Heterozygote Mice Display an Increase in Myocardial Injury and Inflammation after Ischemia\/Reperfusion. Antioxidants, 12.","DOI":"10.3390\/antiox12040921"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.yjmcc.2014.11.008","article-title":"Transgenic overexpression of mitofilin attenuates diabetes mellitus-associated cardiac and mitochondria dysfunction","volume":"79","author":"Thapa","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.transproceed.2023.03.088","article-title":"Infarct Size With Incremental Global Myocardial Ischemia Times: Cyclosporine A in Donation After Circulatory Death Rat Hearts","volume":"55","author":"Quader","year":"2023","journal-title":"Transplant. Proc."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ferrera, R., V\u00e9d\u00e8re, M., Lo-Grasso, M., Augeul, L., Chouabe, C., Bidaux, G., and Baetz, D. (2022). Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD). Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112858"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Arnold, M., M\u00e9ndez-Carmona, N., Gulac, P., Wyss, R.K., Rutishauser, N., Segiser, A., Carrel, T., and Longnus, S. (2020). Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030964"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/jb\/mvm143","article-title":"Characteristics of mitochondrial calpains","volume":"142","author":"Ozaki","year":"2007","journal-title":"J. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00395-022-00948-1","article-title":"Mitochondrial calpain-1 activates NLRP3 inflammasome by cleaving ATP5A1 and inducing mitochondrial ROS in CVB3-induced myocarditis","volume":"117","author":"Liu","year":"2022","journal-title":"Basic Res. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/s41401-020-00526-y","article-title":"Targeted inhibition of calpain in mitochondria alleviates oxidative stress-induced myocardial injury","volume":"42","author":"Zheng","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1161\/CIRCULATIONAHA.124.069329","article-title":"Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development","volume":"151","author":"Wang","year":"2025","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/cvr\/cvs232","article-title":"Contribution of calpains to myocardial ischaemia\/reperfusion injury","volume":"96","author":"Inserte","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27480","DOI":"10.1074\/jbc.M112.358929","article-title":"Deficiency of Capn4 gene inhibits nuclear factor-kappaB (NF-kappaB) protein signaling\/inflammation and reduces remodeling after myocardial infarction","volume":"287","author":"Ma","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.yjmcc.2010.02.024","article-title":"Calpain translocation and activation as pharmacological targets during myocardial ischemia\/reperfusion","volume":"49","author":"Hernando","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"H1690","DOI":"10.1152\/ajpheart.00666.2004","article-title":"Calpain inhibitor-1 protects the rat heart from ischemia-reperfusion injury: Analysis by mechanical work and energetics","volume":"288","author":"Yoshikawa","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, M., Wang, G., and Peng, T. (2021). Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease. Cells, 10.","DOI":"10.3390\/cells10082024"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jss.2020.08.020","article-title":"Modulation of Interleukin-1 and -18 Mediated Injury in Donation after Circulatory Death Mouse Hearts","volume":"257","author":"Quader","year":"2021","journal-title":"J. Surg. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4142203","DOI":"10.1161\/circ.150.suppl_1.4142203","article-title":"Reducing reperfusion injury in circulatory death hearts with calpain inhibitor","volume":"150","author":"Chen","year":"2024","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.cardiores.2006.02.017","article-title":"Ischemic preconditioning prevents calpain-mediated impairment of Na+\/K+-ATPase activity during early reperfusion","volume":"70","author":"Inserte","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1021\/bi061504y","article-title":"Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or maitotoxin-stimulated cells","volume":"46","author":"Glantz","year":"2007","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kiernan, Z., Labate, G., Chen, Q., and Quader, M. (2025). Reducing mitochondrial dysfunction through combination therapy to limit ischemia-reperfusion injury in male DCD rats. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1625385"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10387","DOI":"10.1038\/s41598-022-14320-9","article-title":"Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NT(1)-fragment domains in cardiomyocytes","volume":"12","author":"Weninger","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e23404","DOI":"10.1096\/fj.202301158RR","article-title":"Acute endoplasmic reticulum stress-induced mitochondria respiratory chain damage: The role of activated calpains","volume":"38","author":"Chen","year":"2024","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"H57","DOI":"10.1152\/ajpheart.00478.2022","article-title":"Influence of sex on global myocardial ischemia tolerance and mitochondrial function in circulatory death donor hearts","volume":"324","author":"Chen","year":"2023","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"C910","DOI":"10.1152\/ajpcell.00190.2019","article-title":"Inhibition of the ubiquitous calpains protects complex I activity and enables improved mitophagy in the heart following ischemia-reperfusion","volume":"317","author":"Chen","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.resuscitation.2017.03.033","article-title":"Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs","volume":"116","author":"Matsuura","year":"2017","journal-title":"Resuscitation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nature03434","article-title":"Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death","volume":"434","author":"Baines","year":"2005","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"914","DOI":"10.18632\/aging.100252","article-title":"Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy","volume":"2","author":"Hafner","year":"2010","journal-title":"Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5972","DOI":"10.1038\/s44318-024-00259-2","article-title":"Cyclophilin D plays a critical role in the survival of senescent cells","volume":"43","author":"Protasoni","year":"2024","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1016\/j.bbamcr.2009.10.002","article-title":"Mitochondrial m-calpain plays a role in the release of truncated apoptosis-inducing factor from the mitochondria","volume":"1793","author":"Ozaki","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ijcard.2015.06.010","article-title":"Mitochondrial m-calpain opens the mitochondrial permeability transition pore in ischemia-reperfusion","volume":"197","author":"Yoshida","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/s41418-023-01187-0","article-title":"Identity, structure, and function of the mitochondrial permeability transition pore: Controversies, consensus, recent advances, and future directions","volume":"30","author":"Bernardi","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Endlicher, R., Drahota, Z., \u0160tefkov\u00e1, K., \u010cervinkov\u00e1, Z., and Ku\u010dera, O. (2023). The Mitochondrial Permeability Transition Pore-Current Knowledge of Its Structure, Function, and Regulation, and Optimized Methods for Evaluating Its Functional State. Cells, 12.","DOI":"10.3390\/cells12091273"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00395-019-0726-1","article-title":"Increased calpain-1 in mitochondria induces dilated heart failure in mice: Role of mitochondrial superoxide anion","volume":"114","author":"Cao","year":"2019","journal-title":"Basic Res. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.yjmcc.2009.02.021","article-title":"What is the mitochondrial permeability transition pore?","volume":"46","author":"Halestrap","year":"2009","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/S0008-6363(03)00533-9","article-title":"Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection","volume":"61","author":"Halestrap","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Akande, O., Chen, Q., Toldo, S., Lesnefsky, E.J., and Quader, M. (2020). Ischemia and reperfusion injury to mitochondria and cardiac function in donation after circulatory death hearts- an experimental study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243504"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/nar\/27.8.1935","article-title":"Age-associated increase in 8-oxo-deoxyguanosine glycosylase\/AP lyase activity in rat mitochondria","volume":"27","author":"Croteau","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e13187","DOI":"10.1111\/acel.13187","article-title":"Aging is associated with a decline in Atg9b-mediated autophagosome formation and appearance of enlarged mitochondria in the heart","volume":"19","author":"Liang","year":"2020","journal-title":"Aging Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"H183","DOI":"10.1152\/ajpheart.00708.2014","article-title":"Mending a broken heart: The role of mitophagy in cardioprotection","volume":"308","author":"Moyzis","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1080\/15548627.2019.1659612","article-title":"SQSTM1\/p62 and PPARGC1A\/PGC-1alpha at the interface of autophagy and vascular senescence","volume":"16","author":"Salazar","year":"2020","journal-title":"Autophagy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101935","DOI":"10.1016\/j.arr.2023.101935","article-title":"Pleiotropic and multi-systemic actions of physical exercise on PGC-1\u03b1 signaling during the aging process","volume":"87","author":"Neto","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Protasoni, M., and Zeviani, M. (2021). Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020586"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/FJC.0000000000001424","article-title":"Electron Transport Chain Inhibition to Decrease Injury in Transplanted Donation After Circulatory Death Rat Hearts","volume":"81","author":"Quader","year":"2023","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_63","first-page":"H653","article-title":"Depression of regional blood flow and wall thickening after brief coronary occlusions","volume":"234","author":"Heyndrickx","year":"1978","journal-title":"Am. J. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"I314","DOI":"10.1161\/hc37t1.094853","article-title":"Time course of functional recovery of stunned and hibernating segments after surgical revascularization","volume":"104","author":"Bax","year":"2001","journal-title":"Circulation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1152\/physrev.1999.79.2.609","article-title":"Molecular and cellular mechanisms of myocardial stunning","volume":"79","author":"Bolli","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/s41419-020-02864-5","article-title":"Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion","volume":"11","author":"Hurst","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"113765","DOI":"10.1016\/j.jep.2020.113765","article-title":"Aconitine attenuates mitochondrial dysfunction of cardiomyocytes via promoting deacetylation of cyclophilin-D mediated by sirtuin-3","volume":"270","author":"Wang","year":"2021","journal-title":"J. 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