{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:44:47Z","timestamp":1791801887666,"version":"4.3.4"},"reference-count":62,"publisher":"SAGE Publications","issue":"16-18","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the National Natural Science Foundation of China","award":["82002085"],"award-info":[{"award-number":["82002085"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Mitochondrial oxidative damage is one of the factors that contributes to the pathological process of intestinal ischemia\/reperfusion (II\/R) injury. Glutaredoxin (GRX2), which serves as a crucial protein in maintaining mitochondrial redox homeostasis, affects the activity of downstream proteins through its deglutathionylation effect. Silent information regulator (SIRT3), a crucial deacetylase in mitochondria, has regulatory effects on the activity of various mitochondrial antioxidant enzymes. However, the precise regulatory mechanism underlying SIRT3 enzymatic activity is unknown. Our research is designed to explore GRX2-mediated SIRT3 deglutathionylation\u2019s role and mechanism in II\/R injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      GRX2 levels decreased after II\/R injury, and GRX2 overexpression alleviated II\/R-induced intestinal mucosal injury, mitochondrial oxidative damage, damage to mitochondrial structure and function, remote organ injury, and the systemic inflammatory response. GRX2 overexpression substantially decreased the S-glutathionylation of SIRT3 and increased its activity. The results of the incubation of recombinant SIRT3 with glutathione and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      indicated that the S-glutathionylation of SIRT3 inhibited SIRT3 activity. Subsequently, SIRT3 mutant plasmids with cysteine-to-serine substitutions were constructed to screen for the S-glutathionylation sites of SIRT3 among the four cysteine residues in its amino acid sequence. The results demonstrated that C280 and C283 are the SIRT3 S-glutathionylation sites. The results of experiments using ischemic intestines from clinical cases confirmed the relationship between GRX2 and SIRT3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>This study demonstrates that GRX2 alleviates mitochondrial oxidative damage following II\/R by reversing the S-glutathionylation of SIRT3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      GRX2 is an important protective factor against II\/R injury, and GRX2-mediated deglutathionylation of SIRT3 alleviates II\/R-induced mitochondrial injury and intestinal damage.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 721\u2013738.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261476884","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T01:56:46Z","timestamp":1786413406000},"page":"721-738","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["GRX2-Mediated Deglutathionylation of SIRT3 Alleviates Intestinal Ischemia\/Reperfusion-Induced Mitochondrial Oxidative Damage"],"prefix":"10.1177","volume":"45","author":[{"given":"Liangyuan","family":"Yin","sequence":"first","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhecheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuzi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shili","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjun","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-0052","authenticated-orcid":false,"given":"Xiaofeng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28433-2"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.009"},{"key":"e_1_3_3_4_1","first-page":"1867","article-title":"Glutaredoxin-2 and Sirtuin-3 deficiencies impair cardiac mitochondrial energetics but their effects are not additive","author":"Boardman NT","year":"2021","unstructured":"Boardman NT, , Migally B, , Pileggi C, et al. Glutaredoxin-2 and Sirtuin-3 deficiencies impair cardiac mitochondrial energetics but their effects are not additive. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2021:1867.","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.05.024"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313753110"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2025.2551680"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.12.006"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1970.01340280030009"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39664-2"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-025-00413-4"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310933"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315767"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2002.125718"},{"key":"e_1_3_3_15_1","first-page":"26","article-title":"Identification of SIRT3 as an eraser of H4K16la","author":"Fan Z","year":"2023","unstructured":"Fan Z, , Liu Z, , Zhang N, et al. Identification of SIRT3 as an eraser of H4K16la. iScience 2023:26.","journal-title":"iScience"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2791"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.144"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45808-9"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.561724"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08778"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202256052"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.059631"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.014928"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.05.024"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.10.019"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.07.007"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.101065"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102676"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107428"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101632"},{"key":"e_1_3_3_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0299-4"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.174534"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47623-8"},{"key":"e_1_3_3_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.854994"},{"key":"e_1_3_3_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.10.011"},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2021.04.008"},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-189639"},{"key":"e_1_3_3_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.02.002"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103201"},{"key":"e_1_3_3_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7963"},{"key":"e_1_3_3_41_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000086896.90343.13"},{"key":"e_1_3_3_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1142"},{"key":"e_1_3_3_43_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444913015448"},{"key":"e_1_3_3_44_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.281894"},{"key":"e_1_3_3_45_1","article-title":"The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions","volume":"22","author":"Parent CA","year":"2024","unstructured":"Parent CA, , Fasciani I, , Petragnano F, et al. The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions. PLOS Biology, 2024;22.","journal-title":"PLOS Biology"},{"key":"e_1_3_3_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01816-1"},{"key":"e_1_3_3_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13454"},{"key":"e_1_3_3_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102277"},{"key":"e_1_3_3_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103116"},{"key":"e_1_3_3_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.11.011"},{"key":"e_1_3_3_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.04.008"},{"key":"e_1_3_3_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101343"},{"key":"e_1_3_3_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108940"},{"key":"e_1_3_3_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.09.011"},{"key":"e_1_3_3_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.07.006"},{"issue":"17","key":"e_1_3_3_56_1","article-title":"SIRT3\u2010Mediated Deacetylation of DRP1K711 prevents mitochondrial dysfunction in Parkinson\u2019s disease","volume":"12","author":"Xi Y","year":"2025","unstructured":"Xi Y, , Tao K, , Wen X, et al. SIRT3\u2010Mediated Deacetylation of DRP1K711 prevents mitochondrial dysfunction in Parkinson\u2019s disease. Advanced Science 2025;12(17).","journal-title":"Advanced Science"},{"key":"e_1_3_3_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00399-5"},{"key":"e_1_3_3_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217075"},{"key":"e_1_3_3_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116229"},{"key":"e_1_3_3_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c00383"},{"key":"e_1_3_3_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c13102"},{"key":"e_1_3_3_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.12.038"},{"key":"e_1_3_3_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.06.015"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15230864261476884","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15230864261476884","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15230864261476884","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:47:04Z","timestamp":1791798424000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15230864261476884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":62,"journal-issue":{"issue":"16-18","published-print":{"date-parts":[[2026,12,1]]}},"alternative-id":["10.1177\/15230864261476884"],"URL":"https:\/\/doi.org\/10.1177\/15230864261476884","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}