{"title":"SENP3 通过 FSP1 的去 SUMOylation 使巨噬细胞对铁变态反应敏感","authors":"","doi":"10.1016/j.redox.2024.103267","DOIUrl":null,"url":null,"abstract":"<div><p>Ferroptosis, driven by an imbalance in redox homeostasis, has recently been identified to regulate macrophage function and inflammatory responses. SENP3 is a redox-sensitive de-SUMOylation protease that plays an important role in macrophage function. However, doubt remains on whether SENP3 and SUMOylation regulate macrophage ferroptosis. For the first time, the results of our study suggest that SENP3 sensitizes macrophages to RSL3-induced ferroptosis. We showed that SENP3 promotes the ferroptosis of M2 macrophages to decrease M2 macrophage proportion in vivo. Mechanistically, we identified the ferroptosis repressor FSP1 as a substrate for SUMOylation and confirmed that SUMOylation takes place mainly at its K162 site. We found that SENP3 sensitizes macrophages to ferroptosis by interacting with and de-SUMOylating FSP1 at the K162 site. In summary, our study describes a novel type of posttranslational modification for FSP1 and advances our knowledge of the biological functions of SENP3 and SUMOylation in macrophage ferroptosis.</p></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":null,"pages":null},"PeriodicalIF":10.7000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213231724002453/pdfft?md5=88defba8848bfa2e1e60ef78de5eedd0&pid=1-s2.0-S2213231724002453-main.pdf","citationCount":"0","resultStr":"{\"title\":\"SENP3 sensitizes macrophages to ferroptosis via de-SUMOylation of FSP1\",\"authors\":\"\",\"doi\":\"10.1016/j.redox.2024.103267\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Ferroptosis, driven by an imbalance in redox homeostasis, has recently been identified to regulate macrophage function and inflammatory responses. SENP3 is a redox-sensitive de-SUMOylation protease that plays an important role in macrophage function. However, doubt remains on whether SENP3 and SUMOylation regulate macrophage ferroptosis. For the first time, the results of our study suggest that SENP3 sensitizes macrophages to RSL3-induced ferroptosis. We showed that SENP3 promotes the ferroptosis of M2 macrophages to decrease M2 macrophage proportion in vivo. Mechanistically, we identified the ferroptosis repressor FSP1 as a substrate for SUMOylation and confirmed that SUMOylation takes place mainly at its K162 site. We found that SENP3 sensitizes macrophages to ferroptosis by interacting with and de-SUMOylating FSP1 at the K162 site. In summary, our study describes a novel type of posttranslational modification for FSP1 and advances our knowledge of the biological functions of SENP3 and SUMOylation in macrophage ferroptosis.</p></div>\",\"PeriodicalId\":20998,\"journal\":{\"name\":\"Redox Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2024-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2213231724002453/pdfft?md5=88defba8848bfa2e1e60ef78de5eedd0&pid=1-s2.0-S2213231724002453-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Redox Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213231724002453\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213231724002453","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
SENP3 sensitizes macrophages to ferroptosis via de-SUMOylation of FSP1
Ferroptosis, driven by an imbalance in redox homeostasis, has recently been identified to regulate macrophage function and inflammatory responses. SENP3 is a redox-sensitive de-SUMOylation protease that plays an important role in macrophage function. However, doubt remains on whether SENP3 and SUMOylation regulate macrophage ferroptosis. For the first time, the results of our study suggest that SENP3 sensitizes macrophages to RSL3-induced ferroptosis. We showed that SENP3 promotes the ferroptosis of M2 macrophages to decrease M2 macrophage proportion in vivo. Mechanistically, we identified the ferroptosis repressor FSP1 as a substrate for SUMOylation and confirmed that SUMOylation takes place mainly at its K162 site. We found that SENP3 sensitizes macrophages to ferroptosis by interacting with and de-SUMOylating FSP1 at the K162 site. In summary, our study describes a novel type of posttranslational modification for FSP1 and advances our knowledge of the biological functions of SENP3 and SUMOylation in macrophage ferroptosis.
期刊介绍:
Redox Biology is the official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe. It is also affiliated with the International Society for Free Radical Research (SFRRI). This journal serves as a platform for publishing pioneering research, innovative methods, and comprehensive review articles in the field of redox biology, encompassing both health and disease.
Redox Biology welcomes various forms of contributions, including research articles (short or full communications), methods, mini-reviews, and commentaries. Through its diverse range of published content, Redox Biology aims to foster advancements and insights in the understanding of redox biology and its implications.