{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:10:47Z","timestamp":1780463447009,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,17]],"date-time":"2021-01-17T00:00:00Z","timestamp":1610841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A2B6001173"],"award-info":[{"award-number":["2018R1A2B6001173"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>S\u2010nitrosoglutathione reductase (GSNOR), a protein denitrosylase, protects the mitochondria from mitochondrial nitrosative stress. Mammalian preimplantation embryos are mitochondria\u2010rich, but the effects of GSNOR on mitochondrial function in preimplantation embryos are not well\u2010studied. In the present study, we investigate whether GSNOR plays a role in mitochondrial regulation during porcine preimplantation embryo development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>GSNOR dsRNA was employed to knock down the expression of GSNOR, and N\u03c9\u2010Nitro\u2010L\u2010arginine methyl ester hydrochloride (L\u2010NAME), a pan\u2010NOS inhibitor, was used to prevent protein S\u2010nitrosylation. Mitochondrial amount and function in embryo development were assessed by performing immunofluorescence staining, Western blot, fluorescent probe and real\u2010time reverse transcription PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GSNOR knock\u2010down significantly impaired blastocyst formation and quality and markedly induced the increase in protein S\u2010nitrosylation. Notably, GSNOR knock\u2010down\u2010induced overproduction of S\u2010nitrosylation caused mitochondrial dysfunction, including mitochondrial membrane potential depolarization, mitochondria\u2010derived reactive oxygen species (ROS) increase and ATP deficiency. Interestingly, GSNOR knock\u2010down\u2010induced total mitochondrial amount increase, but the ratio of active mitochondria reduction, suggesting that the damaged mitochondria were accumulated and mitochondrial clearance was inhibited. In addition, damaged mitochondria produced more ROS, and caused DNA damage and apoptosis. Importantly, supplementation with L\u2010NAME reverses the increase in S\u2010nitrosylation, accumulation of damaged mitochondria, and oxidative stress\u2010induced cell death. Interestingly, autophagy was downregulated after GSNOR knock\u2010down, but reversed by L\u2010NAME treatment. Thus, GSNOR maintains mitochondrial homeostasis by promoting autophagy and the clearing of damaged mitochondria in porcine preimplantation embryos.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12990","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T06:55:01Z","timestamp":1610952901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["S\u2010nitrosoglutathione reductase maintains mitochondrial homeostasis by promoting clearance of damaged mitochondria in porcine preimplantation embryos"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-1718","authenticated-orcid":false,"given":"Ying\u2010Jie","family":"Niu","sequence":"first","affiliation":[{"name":"Joint International Research Laboratory of Agriculture and Agri\u2010Product Safety, the Ministry of Education of China Yangzhou University Yangzhou China"},{"name":"Department of Animal Science Chungbuk National University Cheongju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4065-0732","authenticated-orcid":false,"given":"Dongjie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Animal Science Chungbuk National University Cheongju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-2698","authenticated-orcid":false,"given":"Xiang\u2010Shun","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Animal Science Chungbuk National University Cheongju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0503-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113319109"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2017.04.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512203200"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22071"},{"key":"e_1_2_9_7_1","first-page":"123","article-title":"Effect of Alpha Lipoic Acid as an Antioxidant Supplement during In Vitro Maturation Medium on Bovine Embryonic Development","volume":"32","author":"Hassan BMS","year":"2017","journal-title":"J Embryo Transfer"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4928"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R111.285742"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/35055104"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.86.pl1"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2018.1487559"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6398"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-013-0045-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2019.134294"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.65"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.109.2.501"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802473R"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.12750\/JARB.35.1.102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12627"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.068"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0531.2008.01275.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20248"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709336105"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1179\/1351000215Y.0000000003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0223"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa4312"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722452115"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.2017021074"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-2637"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319150010"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.12.025"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1260197"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2011.12.008"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.11.028"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0493"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod62.6.1866"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385114-7.00018-0"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr041"},{"key":"e_1_2_9_41_1","first-page":"183","article-title":"Estrogen ameliorates Nomega\u2010nitro\u2010L\u2010arginine methyl ester\u2010induced blood pressure increment in male spontaneously hypertensive rats: the role of cGMP","volume":"47","author":"Yen CH","year":"2004","journal-title":"Chin J Physiol"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev345"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.12750\/JARB.35.1.12"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.12990","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.12990","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.12990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T20:26:47Z","timestamp":1692476807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.12990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,17]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/cpr.12990"],"URL":"https:\/\/doi.org\/10.1111\/cpr.12990","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,17]]},"assertion":[{"value":"2020-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12990"}}