2024年6月3日，郑州大学Jian-Sheng Kang等研究人员合作在《神经科学通报》杂志发表论文，报道了线粒体基因编码电压指示器在麻醉中的开发与应用。

研究人员表示，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（GEVI）。

在研究人员筛选各种GEVI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具有最高的电压敏感性，但荧光较弱。

总之，研究人员获得了四种能够靶向线粒体的GEVI，并将其命名为线粒体电位指示剂1-4（MPI-1-4）。在体内，研究人员利用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。

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

Author: Yang, Run-Zhou, Wang, Dian-Dian, Li, Sen-Miao, Liu, Pei-Pei, Kang, Jian-Sheng

Issue&Volume: 2024-06-03

Abstract: 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.

DOI: 10.1007/s12264-024-01235-w

Source: https://link.springer.com/article/10.1007/s12264-024-01235-w