• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

抑制 VDAC1 寡聚化通过抑制线粒体 ROS 抑制半胱氨酸剥夺诱导的铁死亡。

Inhibition of VDAC1 oligomerization blocks cysteine deprivation-induced ferroptosis via mitochondrial ROS suppression.

机构信息

Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.

Department of Food Science and Technology, College of Science and Convergence Technology, Seoul Women's University, Seoul, Republic of Korea.

出版信息

Cell Death Dis. 2024 Nov 9;15(11):811. doi: 10.1038/s41419-024-07216-1.

DOI:10.1038/s41419-024-07216-1
PMID:39521767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11550314/
Abstract

Ferroptosis, a regulated form of cell death dependent on reactive oxygen species (ROS), is characterized by iron accumulation and lethal lipid peroxidation. Mitochondria serve as the primary source of ROS and thus play a crucial role in ferroptosis initiation and execution. This study highlights the role of mitochondrial ROS and the significance of voltage-dependent anion channel 1 (VDAC1) oligomerization in ferroptosis induced by cysteine deprivation or ferroptosis-inducer RSL3. Our results demonstrate that the mitochondria-targeted antioxidants MitoQ and MitoT effectively block ferroptosis induction and that dysfunction of complex III of the mitochondrial electron transport chain contributes to ferroptosis induction. Pharmacological inhibitors that target VDAC1 oligomerization have emerged as potent suppressors of ferroptosis that reduce mitochondrial ROS production. These findings underscore the critical involvement of mitochondrial ROS production via complex III of the electron transport chain and the essential role of VDAC1 oligomerization in ferroptosis induced by cysteine deprivation or RSL3. This study deepens our understanding of the intricate molecular networks governing ferroptosis and provides insights into the development of novel therapeutic strategies targeting dysregulated cell death pathways.

摘要

铁死亡是一种依赖于活性氧（ROS）的受调控的细胞死亡形式，其特征是铁积累和致命的脂质过氧化。线粒体是 ROS 的主要来源，因此在铁死亡的起始和执行中起着至关重要的作用。本研究强调了线粒体 ROS 的作用以及电压依赖性阴离子通道 1（VDAC1）寡聚化在半胱氨酸剥夺或铁死亡诱导剂 RSL3 诱导的铁死亡中的重要性。我们的结果表明，线粒体靶向抗氧化剂 MitoQ 和 MitoT 可有效阻止铁死亡的诱导，而线粒体电子传递链复合物 III 的功能障碍导致铁死亡的诱导。针对 VDAC1 寡聚化的药理学抑制剂已成为抑制铁死亡的有效抑制剂，可减少线粒体 ROS 的产生。这些发现强调了通过电子传递链复合物 III 产生线粒体 ROS 以及 VDAC1 寡聚化在半胱氨酸剥夺或 RSL3 诱导的铁死亡中的关键作用。本研究加深了我们对调控铁死亡的复杂分子网络的理解，并为针对失调细胞死亡途径的新型治疗策略的开发提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/23cf21f69ca8/41419_2024_7216_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/bd901926acdc/41419_2024_7216_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/d4a4fa8dca3d/41419_2024_7216_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/59ab858e064a/41419_2024_7216_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/f63c6da84d37/41419_2024_7216_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/8e6ef477af15/41419_2024_7216_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/4c733d7e3457/41419_2024_7216_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/5943ce8323a9/41419_2024_7216_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/23cf21f69ca8/41419_2024_7216_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/bd901926acdc/41419_2024_7216_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/d4a4fa8dca3d/41419_2024_7216_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/59ab858e064a/41419_2024_7216_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/f63c6da84d37/41419_2024_7216_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/8e6ef477af15/41419_2024_7216_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/4c733d7e3457/41419_2024_7216_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/5943ce8323a9/41419_2024_7216_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/630a/11550314/23cf21f69ca8/41419_2024_7216_Fig8_HTML.jpg

相似文献

1
Inhibition of VDAC1 oligomerization blocks cysteine deprivation-induced ferroptosis via mitochondrial ROS suppression.抑制 VDAC1 寡聚化通过抑制线粒体 ROS 抑制半胱氨酸剥夺诱导的铁死亡。
Cell Death Dis. 2024 Nov 9;15(11):811. doi: 10.1038/s41419-024-07216-1.
2
Inhibition of VDAC1 Protects Against Glutamate-Induced Oxytosis and Mitochondrial Fragmentation in Hippocampal HT22 Cells.VDAC1 抑制可防止海马 HT22 细胞中谷氨酸诱导的氧化细胞凋亡和线粒体碎片化。
Cell Mol Neurobiol. 2019 Jan;39(1):73-85. doi: 10.1007/s10571-018-0634-1. Epub 2018 Nov 12.
3
Quinocetone induces mitochondrial apoptosis in HepG2 cells through ROS-dependent promotion of VDAC1 oligomerization and suppression of Wnt1/β-catenin signaling pathway.喹烯酮通过活性氧依赖促进电压依赖性阴离子通道1寡聚化和抑制Wnt1/β-连环蛋白信号通路诱导肝癌细胞HepG2发生线粒体凋亡。
Food Chem Toxicol. 2017 Jul;105:161-176. doi: 10.1016/j.fct.2017.03.039. Epub 2017 Mar 23.
4
Inhibition of VDAC1 Rescues A -Induced Mitochondrial Dysfunction and Ferroptosis via Activation of AMPK and Wnt/-Catenin Pathways.VDAC1 抑制通过激活 AMPK 和 Wnt/-Catenin 通路挽救 Aβ 诱导的线粒体功能障碍和铁死亡。
Mediators Inflamm. 2023 Feb 10;2023:6739691. doi: 10.1155/2023/6739691. eCollection 2023.
5
Novel Compounds Targeting the Mitochondrial Protein VDAC1 Inhibit Apoptosis and Protect against Mitochondrial Dysfunction.靶向线粒体蛋白电压依赖性阴离子通道1（VDAC1）的新型化合物可抑制细胞凋亡并预防线粒体功能障碍。
J Biol Chem. 2016 Nov 25;291(48):24986-25003. doi: 10.1074/jbc.M116.744284. Epub 2016 Oct 13.
6
VDAC1-interacting anion transport inhibitors inhibit VDAC1 oligomerization and apoptosis.与电压依赖性阴离子通道1（VDAC1）相互作用的阴离子转运抑制剂可抑制VDAC1寡聚化及细胞凋亡。
Biochim Biophys Acta. 2016 Jul;1863(7 Pt A):1612-23. doi: 10.1016/j.bbamcr.2016.04.002. Epub 2016 Apr 8.
7
Protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury.通过抑制 VDAC1 寡聚化来保护线粒体可减轻对乙酰氨基酚诱导的急性肝损伤中的铁死亡。
Cell Biol Toxicol. 2022 Jun;38(3):505-530. doi: 10.1007/s10565-021-09624-x. Epub 2021 Aug 17.
8
Dynasore Blocks Ferroptosis through Combined Modulation of Iron Uptake and Inhibition of Mitochondrial Respiration.Dynasore 通过联合调控铁摄取和抑制线粒体呼吸来阻断铁死亡。
Cells. 2020 Oct 9;9(10):2259. doi: 10.3390/cells9102259.
9
Role of mitochondrial reactive oxygen species in chemically-induced ferroptosis.线粒体活性氧在化学诱导的铁死亡中的作用。
Free Radic Biol Med. 2024 Oct;223:473-492. doi: 10.1016/j.freeradbiomed.2024.07.006. Epub 2024 Jul 9.
10
The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis.钙在电压依赖性阴离子通道1（VDAC1）寡聚化及线粒体介导的细胞凋亡中的作用。
Biochim Biophys Acta. 2013 Jul;1833(7):1745-54. doi: 10.1016/j.bbamcr.2013.03.017. Epub 2013 Mar 28.

引用本文的文献

1
Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and Therapeutic Targets.心血管疾病中的线粒体转运蛋白：代谢守门人、致病介质和治疗靶点
Int J Mol Sci. 2025 Aug 31;26(17):8475. doi: 10.3390/ijms26178475.
2
Macrophages and macrophage extracellular vesicles confer cancer ferroptosis resistance via PRDX6-mediated mitophagy inhibition.巨噬细胞和巨噬细胞外囊泡通过PRDX6介导的线粒体自噬抑制赋予癌症铁死亡抗性。
Redox Biol. 2025 Aug 16;86:103826. doi: 10.1016/j.redox.2025.103826.
3
A Membrane-Disruptive Action of VBIT-4 Challenges Its Role as a Widely Used VDAC Oligomerization Inhibitor.

本文引用的文献

1
The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions.铁死亡在癌症中的作用：肿瘤抑制、肿瘤微环境和治疗干预。
Cancer Cell. 2024 Apr 8;42(4):513-534. doi: 10.1016/j.ccell.2024.03.011.
2
Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies.铁死亡在癌症中的作用：从分子机制到治疗策略。
Signal Transduct Target Ther. 2024 Mar 8;9(1):55. doi: 10.1038/s41392-024-01769-5.
3
The diversified role of mitochondria in ferroptosis in cancer.线粒体在癌症中铁死亡中的多样化作用。
VBIT-4的膜破坏作用对其作为广泛使用的电压依赖性阴离子通道寡聚化抑制剂的作用提出了挑战。
bioRxiv. 2025 Jul 3:2025.06.30.661942. doi: 10.1101/2025.06.30.661942.
4
Glutathione Decreases Parkinsonism-Induced Ferroptosis and Oxidative Stress Through the Inhibition of the TRPM2 Channel in Neuronal Cells.谷胱甘肽通过抑制神经元细胞中的TRPM2通道减少帕金森病诱导的铁死亡和氧化应激。
Pharmacol Res Perspect. 2025 Jun;13(3):e70105. doi: 10.1002/prp2.70105.
5
Naringin Suppresses CoCl-Induced Ferroptosis in ARPE-19 Cells.柚皮苷抑制氯化钴诱导的ARPE-19细胞铁死亡。
Antioxidants (Basel). 2025 Feb 18;14(2):236. doi: 10.3390/antiox14020236.
6
GV1001, hTERT Peptide Fragment, Prevents Doxorubicin-Induced Endothelial-to-Mesenchymal Transition in Human Endothelial Cells and Atherosclerosis in Mice.GV1001，人端粒酶逆转录酶肽片段，可预防阿霉素诱导的人内皮细胞内皮-间充质细胞转化及小鼠动脉粥样硬化。
Cells. 2025 Jan 10;14(2):98. doi: 10.3390/cells14020098.
Cell Death Dis. 2023 Aug 14;14(8):519. doi: 10.1038/s41419-023-06045-y.
4
Ferroptosis as a potential target for cancer therapy.铁死亡作为癌症治疗的一个潜在靶点。
Cell Death Dis. 2023 Jul 24;14(7):460. doi: 10.1038/s41419-023-05930-w.
5
HNF4A-BAP31-VDAC1 axis synchronously regulates cell proliferation and ferroptosis in gastric cancer.HNF4A-BAP31-VDAC1 轴同步调节胃癌中的细胞增殖和铁死亡。
Cell Death Dis. 2023 Jun 9;14(6):356. doi: 10.1038/s41419-023-05868-z.
6
Inhibition of VDAC1 Rescues A -Induced Mitochondrial Dysfunction and Ferroptosis via Activation of AMPK and Wnt/-Catenin Pathways.VDAC1 抑制通过激活 AMPK 和 Wnt/-Catenin 通路挽救 Aβ 诱导的线粒体功能障碍和铁死亡。
Mediators Inflamm. 2023 Feb 10;2023:6739691. doi: 10.1155/2023/6739691. eCollection 2023.
7
Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer's disease protects against mitochondrial dysfunction and mitigates brain pathology.靶向阿尔茨海默病小鼠模型中线粒体过度表达的蛋白 VDAC1 可预防线粒体功能障碍并减轻脑病理学改变。
Transl Neurodegener. 2022 Dec 28;11(1):58. doi: 10.1186/s40035-022-00329-7.
8
Emerging roles of ferroptosis in cardiovascular diseases.铁死亡在心血管疾病中的新作用。
Cell Death Discov. 2022 Sep 20;8(1):394. doi: 10.1038/s41420-022-01183-2.
9
Ferroptosis in cancer therapy: a novel approach to reversing drug resistance.铁死亡在癌症治疗中的作用：逆转耐药性的新策略
Mol Cancer. 2022 Feb 12;21(1):47. doi: 10.1186/s12943-022-01530-y.
10
Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells.能量代谢在肿瘤细胞铁死亡调控中的新兴作用。
Adv Sci (Weinh). 2021 Nov;8(22):e2100997. doi: 10.1002/advs.202100997. Epub 2021 Oct 10.