Ayush Srivastava, Maximilian Beyer, Colby Hladun, Rebekah Tardif, Aneeta Arshad, Costel C Darie, Yeonni Zoo, Georgia C Papaefthymiou, Weijing Liu, Rosa Viner, Paolo Arosio, Fadi Bou-Abdallah
{"title":"NCOA4片段（383-522）中铁硫团簇的表征及其与铁蛋白的相互作用。","authors":"Ayush Srivastava, Maximilian Beyer, Colby Hladun, Rebekah Tardif, Aneeta Arshad, Costel C Darie, Yeonni Zoo, Georgia C Papaefthymiou, Weijing Liu, Rosa Viner, Paolo Arosio, Fadi Bou-Abdallah","doi":"10.1021/acschembio.4c00877","DOIUrl":null,"url":null,"abstract":"<p><p>Ferritin degradation pathways, particularly NCOA4-mediated ferritinophagy, are crucial for maintaining iron homeostasis. Here, we demonstrate the coexistence of two NCOA4 isoforms, one iron-sulfur cluster-free and one iron-sulfur cluster-bound, in oxygenated cell cultures. Using a combination of spectroscopic and analytical techniques, in vitro characterization of the NCOA4 fragment (383-522), denoted NCOA4-D, revealed a predominance of monomeric species with a relatively stable [2Fe-2S] cluster under normoxic conditions. The results demonstrate distinct interactions between NCOA4-D isoforms and ferritin, underscoring the influence of cellular oxygen and iron concentrations on NCOA4's regulatory functions, pathways, and ferritin's fate. Our findings suggest that different NCOA4-initiated degradation pathways may concurrently occur in cells and highlight the necessity of further exploring the role of the Fe-S cluster in NCOA4 as an iron-sensing mechanism for maintaining cellular iron homeostasis.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"731-745"},"PeriodicalIF":3.5000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characterization of the Iron-Sulfur Cluster in the NCOA4 Fragment (383-522) and Its Interaction with Ferritin.\",\"authors\":\"Ayush Srivastava, Maximilian Beyer, Colby Hladun, Rebekah Tardif, Aneeta Arshad, Costel C Darie, Yeonni Zoo, Georgia C Papaefthymiou, Weijing Liu, Rosa Viner, Paolo Arosio, Fadi Bou-Abdallah\",\"doi\":\"10.1021/acschembio.4c00877\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ferritin degradation pathways, particularly NCOA4-mediated ferritinophagy, are crucial for maintaining iron homeostasis. Here, we demonstrate the coexistence of two NCOA4 isoforms, one iron-sulfur cluster-free and one iron-sulfur cluster-bound, in oxygenated cell cultures. Using a combination of spectroscopic and analytical techniques, in vitro characterization of the NCOA4 fragment (383-522), denoted NCOA4-D, revealed a predominance of monomeric species with a relatively stable [2Fe-2S] cluster under normoxic conditions. The results demonstrate distinct interactions between NCOA4-D isoforms and ferritin, underscoring the influence of cellular oxygen and iron concentrations on NCOA4's regulatory functions, pathways, and ferritin's fate. Our findings suggest that different NCOA4-initiated degradation pathways may concurrently occur in cells and highlight the necessity of further exploring the role of the Fe-S cluster in NCOA4 as an iron-sensing mechanism for maintaining cellular iron homeostasis.</p>\",\"PeriodicalId\":11,\"journal\":{\"name\":\"ACS Chemical Biology\",\"volume\":\" \",\"pages\":\"731-745\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-03-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Chemical Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1021/acschembio.4c00877\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acschembio.4c00877","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Characterization of the Iron-Sulfur Cluster in the NCOA4 Fragment (383-522) and Its Interaction with Ferritin.
Ferritin degradation pathways, particularly NCOA4-mediated ferritinophagy, are crucial for maintaining iron homeostasis. Here, we demonstrate the coexistence of two NCOA4 isoforms, one iron-sulfur cluster-free and one iron-sulfur cluster-bound, in oxygenated cell cultures. Using a combination of spectroscopic and analytical techniques, in vitro characterization of the NCOA4 fragment (383-522), denoted NCOA4-D, revealed a predominance of monomeric species with a relatively stable [2Fe-2S] cluster under normoxic conditions. The results demonstrate distinct interactions between NCOA4-D isoforms and ferritin, underscoring the influence of cellular oxygen and iron concentrations on NCOA4's regulatory functions, pathways, and ferritin's fate. Our findings suggest that different NCOA4-initiated degradation pathways may concurrently occur in cells and highlight the necessity of further exploring the role of the Fe-S cluster in NCOA4 as an iron-sensing mechanism for maintaining cellular iron homeostasis.
期刊介绍：
ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology.
The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies.
We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.
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