下调高尔基体蛋白 ACBD3 可使细胞对铁变态反应敏感。

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Ying Qian, Shanchuan Ma, Rong Qiu, Zhiyang Sun, Wei Liu, Fan Wu, Sin Man Lam, Zhengguo Xia, Kezhen Wang, Linshen Fang, Guanghou Shui, Xinwang Cao
{"title":"下调高尔基体蛋白 ACBD3 可使细胞对铁变态反应敏感。","authors":"Ying Qian,&nbsp;Shanchuan Ma,&nbsp;Rong Qiu,&nbsp;Zhiyang Sun,&nbsp;Wei Liu,&nbsp;Fan Wu,&nbsp;Sin Man Lam,&nbsp;Zhengguo Xia,&nbsp;Kezhen Wang,&nbsp;Linshen Fang,&nbsp;Guanghou Shui,&nbsp;Xinwang Cao","doi":"10.1002/cbin.12213","DOIUrl":null,"url":null,"abstract":"<p>Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. <i>ACBD3</i> knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to <i>ACBD3</i> knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, <i>ACBD3</i> knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 10","pages":"1559-1572"},"PeriodicalIF":3.3000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis\",\"authors\":\"Ying Qian,&nbsp;Shanchuan Ma,&nbsp;Rong Qiu,&nbsp;Zhiyang Sun,&nbsp;Wei Liu,&nbsp;Fan Wu,&nbsp;Sin Man Lam,&nbsp;Zhengguo Xia,&nbsp;Kezhen Wang,&nbsp;Linshen Fang,&nbsp;Guanghou Shui,&nbsp;Xinwang Cao\",\"doi\":\"10.1002/cbin.12213\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. <i>ACBD3</i> knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to <i>ACBD3</i> knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, <i>ACBD3</i> knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.</p>\",\"PeriodicalId\":9806,\"journal\":{\"name\":\"Cell Biology International\",\"volume\":\"48 10\",\"pages\":\"1559-1572\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Biology International\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cbin.12213\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbin.12213","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

铁变态反应是由铁依赖性脂质过氧化驱动的一种细胞死亡形式,正逐渐成为癌症治疗的一个有前途的靶点。它受到调控脂质代谢、铁稳态和氧化还原平衡及相关过程的分子和途径网络的调控。然而,仍有许多调控分子错综复杂地参与了铁突变过程,这些分子仍有待鉴定。在这里,我们发现抑制高尔基体蛋白酰基辅酶A结合域A包含3(ACBD3)会增加Henrieta Lacks细胞和PANC1细胞对铁突变的敏感性。ACBD3 基因敲除可促进铁蛋白吞噬,从而增加游离铁水平。游离铁的增加以及谷胱甘肽过氧化物酶 4 水平的降低导致活性氧和脂质过氧化物的积累。此外,ACBD3 基因敲除还会导致含多不饱和脂肪酸的甘油磷脂水平升高,其机制仍有待阐明。此外,在 ACBD3 下调的细胞中,通过敲除核受体共激活因子 4 或巴佛洛霉素 A1 处理来抑制铁吞噬,也会阻碍铁嗜性。总之,我们的研究结果突显了 ACBD3 在调控细胞对铁吞噬的耐受性中的关键作用,并表明药理调控 ACBD3 水平是一种很有前景的癌症治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. ACBD3 knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to ACBD3 knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, ACBD3 knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信