{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:20:51Z","timestamp":1793532051745,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the mechanism by which quercetin preserves mitochondrial quality control (MQC) in cardiomyocytes subjected to ischemia\u2013reperfusion stress. An enzyme\u2010linked immunosorbent assay was employed in the in vivo experiments to assess myocardial injury markers, measure the transcript levels of SIRT5\/DNAPK\u2010cs\/MLKL during various time intervals of ischemia\u2013reperfusion, and observe structural changes in cardiomyocytes using transmission electron microscopy. In in vitro investigations, adenovirus transfection was employed to establish a gene\u2010modified model of DNA\u2010PKcs, and primary cardiomyocytes were obtained from a mouse model with modified SIRT5 gene. Reverse transcription polymerase chain reaction, laser confocal microscopy, immunofluorescence localization, JC\u20101 fluorescence assay, Seahorse energy analysis, and various other assays were applied to corroborate the regulatory influence of quercetin on the MQC network in cardiomyocytes after ischemia\u2013reperfusion. In vitro experiments demonstrated that ischemia\u2013reperfusion injury caused changes in the structure of the myocardium. It was seen that quercetin had a beneficial effect on the myocardial tissue, providing protection. As the ischemia\u2013reperfusion process continued, the levels of DNA\u2010PKcs\/SIRT5\/MLKL transcripts were also found to change. In vitro investigations revealed that quercetin mitigated cardiomyocyte injury caused by mitochondrial oxidative stress through DNA\u2010PKcs, and regulated mitophagy and mitochondrial kinetics to sustain optimal mitochondrial energy metabolism levels. Quercetin, through SIRT5 desuccinylation, modulated the stability of DNA\u2010PKcs, and together they regulated the \u201cmitophagy\u2010unfolded protein response.\u201d This preserved the integrity of mitochondrial membrane and genome, mitochondrial dynamics, and mitochondrial energy metabolism. Quercetin may operate synergistically to oversee the regulation of mitophagy and the unfolded protein response through DNA\u2010PKcs\u2010SIRT5 interaction.<\/jats:p>","DOI":"10.1002\/ptr.8177","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T20:10:10Z","timestamp":1709755810000},"page":"2496-2517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Quercetin inhibits necroptosis in cardiomyocytes after ischemia\u2013reperfusion via\n                    <scp>DNA\u2010PKcs\u2010SIRT5<\/scp>\n                    \u2010orchestrated mitochondrial quality control"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-9881","authenticated-orcid":false,"given":"Xing","family":"Chang","sequence":"first","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Wang","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanke","family":"Guan","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-2694","authenticated-orcid":false,"given":"Qiaomin","family":"Wu","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Liu","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9243-1769","authenticated-orcid":false,"given":"Ruxiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guang'anmen Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2018.01.003"},{"issue":"7","key":"e_1_2_11_3_1","first-page":"599","article-title":"Long COVID\u201019 and the heart: Is cardiac mitochondria the missing link?","volume":"38","author":"Chang X.","year":"2023","journal-title":"Antioxidants & Redox Signaling"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155313"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154502"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114171"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.60143"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104260"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3154501"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5529913"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5876841"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00586-6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16887"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106487"},{"key":"e_1_2_11_15_1","first-page":"7","article-title":"Mitochondrial Sirtuins in reproduction","volume":"10","author":"Di Emidio G.","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.08.028"},{"issue":"5","key":"e_1_2_11_17_1","first-page":"1273","article-title":"Quercetin attenuates myocardial ischemia\u2010reperfusion injury via downregulation of the HMGB1\u2010TLR4\u2010NF\u2010\u03baB signaling pathway","volume":"10","author":"Dong L. 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