Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Seville, Spain.
Antioxid Redox Signal. 2022 Aug;37(4-6):274-289. doi: 10.1089/ars.2021.0255. Epub 2022 Apr 18.
Acute responses to hypoxia are essential for the survival of mammals. The carotid body (CB), the main arterial chemoreceptor, contains glomus cells with oxygen (O)-sensitive K channels, which are inhibited during hypoxia to trigger adaptive cardiorespiratory reflexes. In this review, recent advances in molecular mechanisms of acute O sensing in CB glomus cells are discussed, with a special focus on the signaling role of mitochondria through regulating cellular redox status. These advances have been achieved thanks to the use of genetically engineered redox-sensitive green fluorescent protein (roGFP) probes, which allowed us to monitor rapid changes in ROS production in real time in different subcellular compartments during hypoxia. This methodology was used in combination with conditional knockout mice models, pharmacological approaches, and transcriptomic studies. We have proposed a mitochondria-to-membrane signaling model of acute O sensing in which HO released in the mitochondrial intermembrane space serves as a signaling molecule to inhibit K channels on the plasma membrane. Changes in mitochondrial reactive oxygen species (ROS) production during acute hypoxia are highly compartmentalized in the submitochondrial regions. The use of redox-sensitive probes targeted to specific compartments is essential to fully understand the role of mitochondrial ROS in acute O sensing. Further studies are needed to specify the ROS and to characterize the target(s) of ROS in chemoreceptor cells during acute hypoxia. These data may also contribute to a more complete understanding of the implication of ROS in acute responses to hypoxia in O-sensing cells in other organs. . 37, 274-289.
急性缺氧反应对哺乳动物的生存至关重要。颈动脉体（CB）是主要的动脉化学感受器，包含对氧气（O）敏感的 K 通道的球细胞，在缺氧期间，这些通道被抑制，从而引发适应性心肺反射。在这篇综述中，讨论了 CB 球细胞中急性 O 感应的分子机制的最新进展，特别强调了线粒体通过调节细胞氧化还原状态的信号作用。这些进展得益于使用遗传工程化的氧化还原敏感的绿色荧光蛋白（roGFP）探针，这使我们能够在实时监测缺氧期间不同亚细胞区室中 ROS 产生的快速变化。该方法与条件性敲除小鼠模型、药理学方法和转录组学研究相结合。我们提出了一个急性 O 感应的线粒体到膜信号模型，其中在线粒体膜间隙中释放的 HO 作为一种信号分子，抑制质膜上的 K 通道。急性缺氧期间线粒体活性氧（ROS）产生的变化在亚线粒体区室中高度分区化。使用针对特定区室的氧化还原敏感探针对于充分理解线粒体 ROS 在急性 O 感应中的作用至关重要。需要进一步的研究来确定 ROS，并在急性缺氧期间描述化学感受器细胞中 ROS 的靶标。这些数据也可能有助于更全面地了解 ROS 在其他器官中 O 感应细胞对急性缺氧反应的影响。37, 274-289。
