• 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

Mfn2 在 ER 中的定位对于其生物能量功能和神经突发育是必要的。

Mfn2 localization in the ER is necessary for its bioenergetic function and neuritic development.

机构信息

Department of Cell Biology, Physiology and Immunology, Celltec-UB, University of Barcelona, Barcelona, Spain.

Institute of Neurosciences, University of Barcelona, Barcelona, Spain.

出版信息

EMBO Rep. 2021 Sep 6;22(9):e51954. doi: 10.15252/embr.202051954. Epub 2021 Jul 23.

DOI:10.15252/embr.202051954
PMID:34296790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8419703/
Abstract

Mfn2 is a mitochondrial fusion protein with bioenergetic functions implicated in the pathophysiology of neuronal and metabolic disorders. Understanding the bioenergetic mechanism of Mfn2 may aid in designing therapeutic approaches for these disorders. Here we show using endoplasmic reticulum (ER) or mitochondria-targeted Mfn2 that Mfn2 stimulation of the mitochondrial metabolism requires its localization in the ER, which is independent of its fusion function. ER-located Mfn2 interacts with mitochondrial Mfn1/2 to tether the ER and mitochondria together, allowing Ca transfer from the ER to mitochondria to enhance mitochondrial bioenergetics. The physiological relevance of these findings is shown during neurite outgrowth, when there is an increase in Mfn2-dependent ER-mitochondria contact that is necessary for correct neuronal arbor growth. Reduced neuritic growth in Mfn2 KO neurons is recovered by the expression of ER-targeted Mfn2 or an artificial ER-mitochondria tether, indicating that manipulation of ER-mitochondria contacts could be used to treat pathologic conditions involving Mfn2.

摘要

Mfn2 是一种线粒体融合蛋白，具有生物能量学功能，与神经元和代谢紊乱的病理生理学有关。了解 Mfn2 的生物能量学机制可能有助于为这些疾病设计治疗方法。在这里，我们使用内质网 (ER) 或线粒体靶向 Mfn2 表明，Mfn2 对线粒体代谢的刺激需要其在 ER 中的定位，这与其融合功能无关。位于 ER 中的 Mfn2 与线粒体 Mfn1/2 相互作用，将 ER 和线粒体连接在一起，允许 Ca 从 ER 转移到线粒体，从而增强线粒体的生物能量学。这些发现的生理相关性在神经突生长过程中得到了体现，此时 Mfn2 依赖性 ER-线粒体接触增加，这对于正确的神经元树突生长是必要的。Mfn2 KO 神经元中神经突生长减少可通过表达 ER 靶向 Mfn2 或人工 ER-线粒体连接物来恢复，表明可以操纵 ER-线粒体接触来治疗涉及 Mfn2 的病理状况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/8a2c39a83381/EMBR-22-e51954-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/482cd92fb3f7/EMBR-22-e51954-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/bcc4a84ea1be/EMBR-22-e51954-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/c64159b97129/EMBR-22-e51954-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/90d323224df7/EMBR-22-e51954-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/6bd084f87ac1/EMBR-22-e51954-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/fb6d63edfe1b/EMBR-22-e51954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/0f613273e5a5/EMBR-22-e51954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/430843fdc502/EMBR-22-e51954-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/219db26b034a/EMBR-22-e51954-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/4cca797a009e/EMBR-22-e51954-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/8a2c39a83381/EMBR-22-e51954-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/482cd92fb3f7/EMBR-22-e51954-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/bcc4a84ea1be/EMBR-22-e51954-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/c64159b97129/EMBR-22-e51954-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/90d323224df7/EMBR-22-e51954-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/6bd084f87ac1/EMBR-22-e51954-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/fb6d63edfe1b/EMBR-22-e51954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/0f613273e5a5/EMBR-22-e51954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/430843fdc502/EMBR-22-e51954-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/219db26b034a/EMBR-22-e51954-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/4cca797a009e/EMBR-22-e51954-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3122/8419703/8a2c39a83381/EMBR-22-e51954-g009.jpg

相似文献

1
Mfn2 localization in the ER is necessary for its bioenergetic function and neuritic development.Mfn2 在 ER 中的定位对于其生物能量功能和神经突发育是必要的。
EMBO Rep. 2021 Sep 6;22(9):e51954. doi: 10.15252/embr.202051954. Epub 2021 Jul 23.
2
Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling.线粒体融合蛋白2缺失增加内质网与线粒体的偶联。
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2174-81. doi: 10.1073/pnas.1504880112. Epub 2015 Apr 13.
3
The role of Mfn2 in the structure and function of endoplasmic reticulum-mitochondrial tethering in vivo.Mfn2 在体内内质网-线粒体连接结构和功能中的作用。
J Cell Sci. 2021 Jul 1;134(13). doi: 10.1242/jcs.253443. Epub 2021 Jul 9.
4
Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria.线粒体融合蛋白2的剪接变体塑造内质网并将其与线粒体相连。
Science. 2023 Jun 23;380(6651):eadh9351. doi: 10.1126/science.adh9351.
5
Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts.Mul1 通过维持内质网-线粒体接触来抑制成熟神经元中 Parkin 介导的线粒体自噬。
Nat Commun. 2019 Aug 13;10(1):3645. doi: 10.1038/s41467-019-11636-5.
6
Polycystin 2 regulates mitochondrial Ca signaling, bioenergetics, and dynamics through mitofusin 2.多囊蛋白 2 通过线粒体融合蛋白 2 调节线粒体钙信号、生物能量和动力学。
Sci Signal. 2019 May 7;12(580):eaat7397. doi: 10.1126/scisignal.aat7397.
7
Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy.Mfn2 通过 PINK1/parkin 的泛素化将 ER 从线粒体中释放出来，从而驱动线粒体自噬。
Elife. 2018 Apr 20;7:e32866. doi: 10.7554/eLife.32866.
8
MTCH2 cooperates with MFN2 and lysophosphatidic acid synthesis to sustain mitochondrial fusion.MTCH2 与 MFN2 合作并促进溶血磷脂酸的合成以维持线粒体融合。
EMBO Rep. 2024 Jan;25(1):45-67. doi: 10.1038/s44319-023-00009-1. Epub 2023 Dec 14.
9
MFN2 mutations in Charcot-Marie-Tooth disease alter mitochondria-associated ER membrane function but do not impair bioenergetics.MFN2 突变导致 Charcot-Marie-Tooth 病改变线粒体相关内质网膜功能，但不损害生物能量学。
Hum Mol Genet. 2019 Jun 1;28(11):1782-1800. doi: 10.1093/hmg/ddz008.
10
MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2.MITOL 通过 Mitofusin2 调节内质网-线粒体接触。
Mol Cell. 2013 Jul 11;51(1):20-34. doi: 10.1016/j.molcel.2013.04.023. Epub 2013 May 30.

引用本文的文献

1
The complex web of membrane contact sites in brain aging and neurodegeneration.大脑衰老和神经退行性变中膜接触位点的复杂网络。
Cell Mol Life Sci. 2025 Aug 8;82(1):301. doi: 10.1007/s00018-025-05830-6.
2
Unraveling mitochondrial crosstalk: a new frontier in heart failure pathogenesis.解析线粒体间的相互作用：心力衰竭发病机制的新前沿。
Front Cardiovasc Med. 2025 Jul 15;12:1641023. doi: 10.3389/fcvm.2025.1641023. eCollection 2025.
3
Mitochondria-Associated Endoplasmic Reticulum Membranes in Human Health and Diseases.人类健康与疾病中的线粒体相关内质网膜

本文引用的文献

1
Measurement of co-localization of objects in dual-colour confocal images.双色共聚焦图像中物体共定位的测量。
J Microsc. 1993 Mar;169(3):375-382. doi: 10.1111/j.1365-2818.1993.tb03313.x.
2
Mitofusin 2 in Macrophages Links Mitochondrial ROS Production, Cytokine Release, Phagocytosis, Autophagy, and Bactericidal Activity.巨噬细胞中的线粒体融合蛋白 2 与线粒体 ROS 产生、细胞因子释放、吞噬作用、自噬和杀菌活性有关。
Cell Rep. 2020 Aug 25;32(8):108079. doi: 10.1016/j.celrep.2020.108079.
3
MFN2 contributes to metabolic disorders and inflammation in the aging of rat chondrocytes and osteoarthritis.
MedComm (2020). 2025 Jun 27;6(7):e70259. doi: 10.1002/mco2.70259. eCollection 2025 Jul.
4
Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles.生理肌肉功能受小鼠骨骼肌中骨骼内源性大麻素系统的控制。
Int J Mol Sci. 2025 May 30;26(11):5291. doi: 10.3390/ijms26115291.
5
Chronic mild stress disrupts mitophagy and mitochondrial status in rat frontal cortex.慢性轻度应激会破坏大鼠前额叶皮质中的线粒体自噬和线粒体状态。
J Transl Med. 2025 May 23;23(1):580. doi: 10.1186/s12967-025-06604-1.
6
Decoding ischemic stroke: Perspectives on the endoplasmic reticulum, mitochondria, and their crosstalk.解读缺血性中风：内质网、线粒体及其相互作用的研究视角
Redox Biol. 2025 May;82:103622. doi: 10.1016/j.redox.2025.103622. Epub 2025 Mar 27.
7
Mitochondria associated membranes in dilated cardiomyopathy: connecting pathogenesis and cellular dysfunction.扩张型心肌病中的线粒体相关膜：连接发病机制与细胞功能障碍
Front Cardiovasc Med. 2025 Mar 17;12:1571998. doi: 10.3389/fcvm.2025.1571998. eCollection 2025.
8
Endogenous interactomes of MFN1 and MFN2 provide novel insights into interorganelle communication and autophagy.MFN1和MFN2的内源性相互作用组为细胞器间通讯和自噬提供了新见解。
Autophagy. 2025 May;21(5):957-978. doi: 10.1080/15548627.2024.2440843. Epub 2024 Dec 24.
9
Dynamic death decisions: How mitochondrial dynamics shape cellular commitment to apoptosis and ferroptosis.动态死亡决策：线粒体动力学如何塑造细胞对细胞凋亡和铁死亡的决定。
Dev Cell. 2024 Oct 7;59(19):2549-2565. doi: 10.1016/j.devcel.2024.09.004.
10
Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER.REEP5-MFN1/2 的动态相互作用使线粒体搭管状内质网的便车。
J Cell Biol. 2024 Oct 7;223(10). doi: 10.1083/jcb.202304031. Epub 2024 Aug 12.
MFN2 促进了大鼠软骨细胞衰老和骨关节炎中的代谢紊乱和炎症。
Osteoarthritis Cartilage. 2020 Aug;28(8):1079-1091. doi: 10.1016/j.joca.2019.11.011. Epub 2020 May 19.
4
The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses.AMPK-MFN2 轴调节能量应激诱导的 MAM 动态和自噬。
Autophagy. 2021 May;17(5):1142-1156. doi: 10.1080/15548627.2020.1749490. Epub 2020 Apr 19.
5
Defective Mitochondrial Pyruvate Flux Affects Cell Bioenergetics in Alzheimer's Disease-Related Models.线粒体丙酮酸通量缺陷影响阿尔茨海默病相关模型中的细胞生物能量学。
Cell Rep. 2020 Feb 18;30(7):2332-2348.e10. doi: 10.1016/j.celrep.2020.01.060.
6
The Charcot-Marie Tooth Disease Mutation R94Q in MFN2 Decreases ATP Production but Increases Mitochondrial Respiration under Conditions of Mild Oxidative Stress.MFN2 中的 Ch arcot-Marie-Tooth 病突变 R94Q 可降低在轻度氧化应激条件下的 ATP 生成，但增加线粒体呼吸。
Cells. 2019 Oct 21;8(10):1289. doi: 10.3390/cells8101289.
7
Mitofusin 2 Is Essential for IP-Mediated SR/Mitochondria Metabolic Feedback in Ventricular Myocytes.线粒体融合蛋白2对于心室肌细胞中肌醇-1,4,5-三磷酸介导的肌浆网/线粒体代谢反馈至关重要。
Front Physiol. 2019 Jul 18;10:733. doi: 10.3389/fphys.2019.00733. eCollection 2019.
8
Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.IRE1α 的非规范功能决定了线粒体相关内质网的组成，以控制钙传递和生物能量。
Nat Cell Biol. 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y. Epub 2019 May 20.
9
ER and Nutrient Stress Promote Assembly of Respiratory Chain Supercomplexes through the PERK-eIF2α Axis.内质网和营养应激通过 PERK-eIF2α 轴促进呼吸链超级复合物的组装。
Mol Cell. 2019 Jun 6;74(5):877-890.e6. doi: 10.1016/j.molcel.2019.03.031. Epub 2019 Apr 22.
10
Blockade of MCU-Mediated Ca Uptake Perturbs Lipid Metabolism via PP4-Dependent AMPK Dephosphorylation.MCU 介导电钙内流阻断通过依赖于 PP4 的 AMPK 去磷酸化作用干扰脂代谢。
Cell Rep. 2019 Mar 26;26(13):3709-3725.e7. doi: 10.1016/j.celrep.2019.02.107.