开发线粒体基因编码电压指示器并将其应用于麻醉。

IF 5.9 2区 医学 Q1 NEUROSCIENCES
Neuroscience bulletin Pub Date : 2024-10-01 Epub Date: 2024-06-03 DOI:10.1007/s12264-024-01235-w
Run-Zhou Yang, Dian-Dian Wang, Sen-Miao Li, Pei-Pei Liu, Jian-Sheng Kang
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引用次数: 0

摘要

线粒体膜电位(MMP)在细胞和细胞器的功能中起着至关重要的作用,涉及各种细胞生理过程,包括能量产生、活性氧(ROS)形成、未折叠蛋白应激和细胞存活。目前,还缺乏针对 MMP 的基因编码荧光指示剂(GEVIs)。在我们筛选各种 GEVIs 监测 MMP 的潜力时,动作电位加速传感器(ASAP)在靶向线粒体方面表现出最佳性能,并对多种细胞类型的去极化具有敏感性。然而,线粒体 ASAP 在心肌细胞中也显示出对 ROS 的敏感性。因此,产生了两个抗 ROS 的 ASAP 突变体。双突变体 ASAP3-ST 的电压灵敏度最高,但荧光较弱。总之,我们获得了四种能够靶向线粒体的 GEVIs,并将其命名为线粒体电位指示剂 1-4(MPI-1-4)。在体内,利用 MPI-2 进行的纤维光度测定实验显示,在异氟醚诱导的 M2 皮层麻醉过程中,线粒体会发生去极化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis.

Development and Application of a Mitochondrial Genetically Encoded Voltage Indicator in Narcosis.

Mitochondrial membrane potential (MMP) plays a crucial role in the function of cells and organelles, involving various cellular physiological processes, including energy production, formation of reactive oxygen species (ROS), unfolded protein stress, and cell survival. Currently, there is a lack of genetically encoded fluorescence indicators (GEVIs) for MMP. In our screening of various GEVIs for their potential monitoring MMP, the Accelerated Sensor of Action Potentials (ASAP) demonstrated optimal performance in targeting mitochondria and sensitivity to depolarization in multiple cell types. However, mitochondrial ASAPs also displayed sensitivity to ROS in cardiomyocytes. Therefore, two ASAP mutants resistant to ROS were generated. A double mutant ASAP3-ST exhibited the highest voltage sensitivity but weaker fluorescence. Overall, four GEVIs capable of targeting mitochondria were obtained and named mitochondrial potential indicators 1-4 (MPI-1-4). In vivo, fiber photometry experiments utilizing MPI-2 revealed a mitochondrial depolarization during isoflurane-induced narcosis in the M2 cortex.

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来源期刊
Neuroscience bulletin
Neuroscience bulletin NEUROSCIENCES-
CiteScore
7.20
自引率
16.10%
发文量
163
审稿时长
6-12 weeks
期刊介绍: Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.
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