Jing Wang, Shuo Li, Haidong Xu, Jie Xue, Xiaorui Wan, Weilong Wu, Jiani Huang, Huiling Zhang, Zhenghong Qin, Yan Wang
{"title":"CDGSH铁硫结构域1在kainic酸诱导的线粒体铁超载、功能障碍和神经元损伤中的作用和机制","authors":"Jing Wang, Shuo Li, Haidong Xu, Jie Xue, Xiaorui Wan, Weilong Wu, Jiani Huang, Huiling Zhang, Zhenghong Qin, Yan Wang","doi":"10.1016/j.biopha.2025.118067","DOIUrl":null,"url":null,"abstract":"<div><div>Maintaining mitochondrial function plays a crucial role in preventing and treating neurodegenerative diseases. CDGSH iron-sulfur domain 1 (CISD1), a NEET family protein localized on the mitochondrial outer membrane, regulates mitochondrial iron transport. However, the precise mechanism by which CISD1 modulates mitochondrial Fe<sup>2 +</sup> remains unclear. In this study, we examine the link between aberrant iron metabolism and mitochondrial dysfunction using <em>in vivo</em> and <em>in vitro</em> excitotoxicity models. Our study also clarifies how CISD1 modulates KA-mediated excitotoxic neuronal damage. Overexpression of CISD1 reverses KA-induced mitochondrial iron overload and dysfunction. KA significantly downregulate the mitochondrial protein deacetylase SIRT1. SRT1460 (SIRT1-specific agonist) mitigates mitochondrial iron overload and restore CISD1 expression levels. Altogether, CISD1 protects against excitotoxic injury by mitigating mitochondrial iron overload, thereby providing a potential therapeutic target for neurodegenerative diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118067"},"PeriodicalIF":6.9000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The roles and mechanisms of CDGSH iron-sulfur domain 1 in kainic acid-induced mitochondrial iron overload, dysfunction and neuronal damage\",\"authors\":\"Jing Wang, Shuo Li, Haidong Xu, Jie Xue, Xiaorui Wan, Weilong Wu, Jiani Huang, Huiling Zhang, Zhenghong Qin, Yan Wang\",\"doi\":\"10.1016/j.biopha.2025.118067\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Maintaining mitochondrial function plays a crucial role in preventing and treating neurodegenerative diseases. CDGSH iron-sulfur domain 1 (CISD1), a NEET family protein localized on the mitochondrial outer membrane, regulates mitochondrial iron transport. However, the precise mechanism by which CISD1 modulates mitochondrial Fe<sup>2 +</sup> remains unclear. In this study, we examine the link between aberrant iron metabolism and mitochondrial dysfunction using <em>in vivo</em> and <em>in vitro</em> excitotoxicity models. Our study also clarifies how CISD1 modulates KA-mediated excitotoxic neuronal damage. Overexpression of CISD1 reverses KA-induced mitochondrial iron overload and dysfunction. KA significantly downregulate the mitochondrial protein deacetylase SIRT1. SRT1460 (SIRT1-specific agonist) mitigates mitochondrial iron overload and restore CISD1 expression levels. Altogether, CISD1 protects against excitotoxic injury by mitigating mitochondrial iron overload, thereby providing a potential therapeutic target for neurodegenerative diseases.</div></div>\",\"PeriodicalId\":8966,\"journal\":{\"name\":\"Biomedicine & Pharmacotherapy\",\"volume\":\"187 \",\"pages\":\"Article 118067\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2025-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedicine & Pharmacotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0753332225002616\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedicine & Pharmacotherapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0753332225002616","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
The roles and mechanisms of CDGSH iron-sulfur domain 1 in kainic acid-induced mitochondrial iron overload, dysfunction and neuronal damage
Maintaining mitochondrial function plays a crucial role in preventing and treating neurodegenerative diseases. CDGSH iron-sulfur domain 1 (CISD1), a NEET family protein localized on the mitochondrial outer membrane, regulates mitochondrial iron transport. However, the precise mechanism by which CISD1 modulates mitochondrial Fe2 + remains unclear. In this study, we examine the link between aberrant iron metabolism and mitochondrial dysfunction using in vivo and in vitro excitotoxicity models. Our study also clarifies how CISD1 modulates KA-mediated excitotoxic neuronal damage. Overexpression of CISD1 reverses KA-induced mitochondrial iron overload and dysfunction. KA significantly downregulate the mitochondrial protein deacetylase SIRT1. SRT1460 (SIRT1-specific agonist) mitigates mitochondrial iron overload and restore CISD1 expression levels. Altogether, CISD1 protects against excitotoxic injury by mitigating mitochondrial iron overload, thereby providing a potential therapeutic target for neurodegenerative diseases.
期刊介绍:
Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.