• 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

L-OPA1独立于膜融合调节线粒体闪光的产生。

L-OPA1 regulates mitoflash biogenesis independently from membrane fusion.

作者信息

Rosselin Manon, Santo-Domingo Jaime, Bermont Flavien, Giacomello Marta, Demaurex Nicolas

机构信息

Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.

Nestlé Institute of Health Sciences SA, EPFL Innovation Park, Lausanne, Switzerland.

出版信息

EMBO Rep. 2017 Mar;18(3):451-463. doi: 10.15252/embr.201642931. Epub 2017 Feb 7.

DOI:10.15252/embr.201642931
PMID:28174208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5331265/
Abstract

Mitochondrial flashes mediated by optic atrophy 1 (OPA1) fusion protein are bioenergetic responses to stochastic drops in mitochondrial membrane potential (Δψ) whose origin is unclear. Using structurally distinct genetically encoded pH-sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed "mitopHlashes". Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during Δψ drops or respiratory chain inhibition. ablation does not alter Δψ fluctuations but drastically decreases the efficiency of mitopHlash/Δψ coupling, which is restored by re-expressing fusion-deficient OPA1 and preserved in cells lacking the outer-membrane fusion proteins MFN1/2 or the OPA1 proteases OMA1 and YME1L, indicating that mitochondrial membrane fusion and OPA1 proteolytic processing are dispensable. pH/Δψ uncoupling occurs early during staurosporine-induced apoptosis and is mitigated by OPA1 overexpression, suggesting that OPA1 maintains mitopHlash competence during stress conditions. We propose that OPA1 stabilizes respiratory chain supercomplexes in a conformation that enables respiring mitochondria to compensate a drop in Δψ by an explosive matrix pH flash.

摘要

由视神经萎缩蛋白1（OPA1）融合蛋白介导的线粒体闪烁是对线粒体膜电位（Δψ）随机下降的生物能量反应，其起源尚不清楚。使用结构不同的基因编码pH敏感探针，我们证实闪烁是基质碱化瞬变，从而确定了这些事件的pH性质，我们将其重新命名为“线粒体pH闪烁”。通过电子显微镜验证位于嵴或膜间隙中的探针在Δψ下降或呼吸链抑制期间未报告pH变化。OPA1缺失不会改变Δψ波动，但会大幅降低线粒体pH闪烁/Δψ偶联的效率，通过重新表达融合缺陷型OPA1可恢复该效率，并且在缺乏外膜融合蛋白MFN1/2或OPA1蛋白酶OMA1和YME1L的细胞中得以保留，这表明线粒体膜融合和OPA1蛋白水解加工是不必要的。pH/Δψ解偶联在星形孢菌素诱导的细胞凋亡早期发生，并通过OPA1过表达得到缓解，这表明OPA1在应激条件下维持线粒体pH闪烁能力。我们提出，OPA1以一种构象稳定呼吸链超复合物，使呼吸的线粒体能够通过爆发性的基质pH闪烁来补偿Δψ的下降。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/dedd2b7053ff/EMBR-18-451-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/9679bdcdaff4/EMBR-18-451-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/d6f05acae84c/EMBR-18-451-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/2fbd0f762b14/EMBR-18-451-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/c2adb679ed97/EMBR-18-451-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/59e64ca018b9/EMBR-18-451-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/cdb4d9c8c7f7/EMBR-18-451-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/e63291bbaf3b/EMBR-18-451-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/933e8d9a953a/EMBR-18-451-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/12e89363633c/EMBR-18-451-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/e5b3eb0ceefe/EMBR-18-451-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/49b5d21c55ae/EMBR-18-451-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/dedd2b7053ff/EMBR-18-451-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/9679bdcdaff4/EMBR-18-451-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/d6f05acae84c/EMBR-18-451-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/2fbd0f762b14/EMBR-18-451-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/c2adb679ed97/EMBR-18-451-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/59e64ca018b9/EMBR-18-451-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/cdb4d9c8c7f7/EMBR-18-451-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/e63291bbaf3b/EMBR-18-451-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/933e8d9a953a/EMBR-18-451-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/12e89363633c/EMBR-18-451-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/e5b3eb0ceefe/EMBR-18-451-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/49b5d21c55ae/EMBR-18-451-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc9b/5331265/dedd2b7053ff/EMBR-18-451-g011.jpg

相似文献

1
L-OPA1 regulates mitoflash biogenesis independently from membrane fusion.L-OPA1独立于膜融合调节线粒体闪光的产生。
EMBO Rep. 2017 Mar;18(3):451-463. doi: 10.15252/embr.201642931. Epub 2017 Feb 7.
2
The short variant of the mitochondrial dynamin OPA1 maintains mitochondrial energetics and cristae structure.线粒体动力蛋白OPA1的短变体维持线粒体能量代谢和嵴结构。
J Biol Chem. 2017 Apr 28;292(17):7115-7130. doi: 10.1074/jbc.M116.762567. Epub 2017 Mar 15.
3
OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion.OPA1独立于线粒体融合调控凋亡性嵴重塑。
Cell. 2006 Jul 14;126(1):177-89. doi: 10.1016/j.cell.2006.06.025.
4
Loss of Drp1 function alters OPA1 processing and changes mitochondrial membrane organization.动力相关蛋白1（Drp1）功能丧失会改变视神经萎缩蛋白1（OPA1）的加工过程，并改变线粒体膜结构。
Exp Cell Res. 2009 Aug 1;315(13):2165-80. doi: 10.1016/j.yexcr.2009.04.016. Epub 2009 May 3.
5
OPA1 processing in cell death and disease - the long and short of it.细胞死亡与疾病中的OPA1加工——其来龙去脉
J Cell Sci. 2016 Jun 15;129(12):2297-306. doi: 10.1242/jcs.159186. Epub 2016 May 17.
6
Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells.氧化应激破坏培养的哺乳动物细胞中线粒体解偶联蛋白 1 介导的线粒体动力学。
Redox Rep. 2018 Dec;23(1):160-167. doi: 10.1080/13510002.2018.1492766.
7
Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial membrane potential.金属蛋白酶介导的OPA1加工受线粒体膜电位调节。
Biol Cell. 2008 May;100(5):315-25. doi: 10.1042/BC20070110.
8
The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission.i-AAA 蛋白酶 YME1L 和 OMA1 切割 OPA1 以平衡线粒体融合和裂变。
J Cell Biol. 2014 Mar 17;204(6):919-29. doi: 10.1083/jcb.201308006. Epub 2014 Mar 10.
9
Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.凋亡素与线粒体外膜融合蛋白相互作用并调节线粒体形态。
J Cell Sci. 2016 Mar 1;129(5):994-1002. doi: 10.1242/jcs.176792. Epub 2016 Jan 26.
10
OPA1 regulates respiratory supercomplexes assembly: The role of mitochondrial swelling.OPA1 调节呼吸超级复合物的组装：线粒体肿胀的作用。
Mitochondrion. 2020 Mar;51:30-39. doi: 10.1016/j.mito.2019.11.006. Epub 2019 Dec 20.

引用本文的文献

1
ShenQiWan ameliorates renal injury in type 2 diabetic mice by modulating mitochondrial fusion and endoplasmic reticulum stress.参芪丸通过调节线粒体融合和内质网应激改善2型糖尿病小鼠的肾损伤。
Front Pharmacol. 2023 Nov 10;14:1265551. doi: 10.3389/fphar.2023.1265551. eCollection 2023.
2
Mitochondrial F F ATP synthase determines the local proton motive force at cristae rims.线粒体 F F ATP 合酶决定嵴边缘的局部质子动力势。
EMBO Rep. 2021 Dec 6;22(12):e52727. doi: 10.15252/embr.202152727. Epub 2021 Sep 30.
3
Advances in the mechanism and treatment of mitochondrial quality control involved in myocardial infarction.

本文引用的文献

1
Mitofilin and CHCHD6 physically interact with Sam50 to sustain cristae structure.线粒体丝状蛋白和卷曲螺旋结构域蛋白6与Sam50发生物理相互作用以维持嵴结构。
Sci Rep. 2015 Nov 4;5:16064. doi: 10.1038/srep16064.
2
Trans-mitochondrial coordination of cristae at regulated membrane junctions.嵴在线粒体膜调控连接处的跨线粒体协调。
Nat Commun. 2015 Feb 17;6:6259. doi: 10.1038/ncomms7259.
3
The 'mitoflash' probe cpYFP does not respond to superoxide.“线粒体闪光”探针cpYFP对超氧化物无反应。
心肌梗死中线粒体质量控制的机制和治疗进展。
J Cell Mol Med. 2021 Aug;25(15):7110-7121. doi: 10.1111/jcmm.16744. Epub 2021 Jun 23.
4
Excitation spectral microscopy for highly multiplexed fluorescence imaging and quantitative biosensing.用于高度多重荧光成像和定量生物传感的激发光谱显微镜。
Light Sci Appl. 2021 May 8;10(1):97. doi: 10.1038/s41377-021-00536-3.
5
Inhibition of the mitochondrial ATPase function by IF1 changes the spatiotemporal organization of ATP synthase.IF1 通过抑制线粒体 ATP 酶的功能改变 ATP 合酶的时空组织。
Biochim Biophys Acta Bioenerg. 2021 Jan 1;1862(1):148322. doi: 10.1016/j.bbabio.2020.148322. Epub 2020 Oct 14.
6
IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.白细胞介素-1诱导白细胞介素-1受体相关激酶2的线粒体易位，以抑制脂肪细胞中的氧化代谢。
Nat Immunol. 2020 Oct;21(10):1219-1231. doi: 10.1038/s41590-020-0750-1. Epub 2020 Aug 10.
7
GDF11 enhances therapeutic efficacy of mesenchymal stem cells for myocardial infarction via YME1L-mediated OPA1 processing.GDF11 通过 YME1L 介导的 OPA1 加工增强间充质干细胞治疗心肌梗死的疗效。
Stem Cells Transl Med. 2020 Oct;9(10):1257-1271. doi: 10.1002/sctm.20-0005. Epub 2020 Jun 9.
8
Development and Application of Sub-Mitochondrial Targeted Ca Biosensors.亚线粒体靶向钙生物传感器的开发与应用
Front Cell Neurosci. 2019 Oct 4;13:449. doi: 10.3389/fncel.2019.00449. eCollection 2019.
9
Identification of an ATP-sensitive potassium channel in mitochondria.鉴定线粒体中的 ATP 敏感性钾通道。
Nature. 2019 Aug;572(7771):609-613. doi: 10.1038/s41586-019-1498-3. Epub 2019 Aug 21.
10
Dynamics of the mitochondrial permeability transition pore: Transient and permanent opening events.线粒体通透性转换孔的动力学：瞬态和持久开放事件。
Arch Biochem Biophys. 2019 May 15;666:31-39. doi: 10.1016/j.abb.2019.03.016. Epub 2019 Mar 28.
Nature. 2014 Oct 23;514(7523):E12-4. doi: 10.1038/nature13858.
4
OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand.OPA1 依赖的嵴调节对于细胞适应代谢需求至关重要。
EMBO J. 2014 Nov 18;33(22):2676-91. doi: 10.15252/embj.201488349. Epub 2014 Oct 8.
5
The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission.i-AAA 蛋白酶 YME1L 和 OMA1 切割 OPA1 以平衡线粒体融合和裂变。
J Cell Biol. 2014 Mar 17;204(6):919-29. doi: 10.1083/jcb.201308006. Epub 2014 Mar 10.
6
Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans.成年早期的 Mitoflash 频率可预测秀丽隐杆线虫的寿命。
Nature. 2014 Apr 3;508(7494):128-32. doi: 10.1038/nature13012. Epub 2014 Feb 12.
7
Lateral pH gradient between OXPHOS complex IV and F(0)F(1) ATP-synthase in folded mitochondrial membranes.折叠线粒体膜中 OXPHOS 复合物 IV 和 F(0)F(1)ATP 合酶之间的横向 pH 梯度。
Nat Commun. 2014;5:3103. doi: 10.1038/ncomms4103.
8
Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency.线粒体嵴的形状决定了呼吸链超级复合物的组装和呼吸效率。
Cell. 2013 Sep 26;155(1):160-71. doi: 10.1016/j.cell.2013.08.032. Epub 2013 Sep 19.
9
OPA1 promotes pH flashes that spread between contiguous mitochondria without matrix protein exchange.OPA1 促进 pH 瞬间波动在相邻线粒体之间传播，而无需基质蛋白交换。
EMBO J. 2013 Jul 3;32(13):1927-40. doi: 10.1038/emboj.2013.124. Epub 2013 May 28.
10
Respective contribution of mitochondrial superoxide and pH to mitochondria-targeted circularly permuted yellow fluorescent protein (mt-cpYFP) flash activity.线粒体超氧化物和 pH 值对线粒体靶向环状荧光蛋白（mt-cpYFP）荧光强度的各自贡献。
J Biol Chem. 2013 Apr 12;288(15):10567-77. doi: 10.1074/jbc.M113.455709. Epub 2013 Mar 1.