Center for Membrane and Cell Physiology, University of Virginia, Charlottesville, Virginia 22908, United States.
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, United States.
Chem Res Toxicol. 2021 Aug 16;34(8):1826-1845. doi: 10.1021/acs.chemrestox.1c00149. Epub 2021 Jul 20.
Redox-active molecules play essential roles in cell homeostasis, signaling, and other biological processes. Dysregulation of redox signaling can lead to toxic effects and subsequently cause diseases. Therefore, real-time tracking of specific redox-signaling molecules in live cells would be critical for deciphering their functional roles in pathophysiology. Fluorescent protein (FP)-based genetically encoded redox indicators (GERIs) have emerged as valuable tools for monitoring the redox states of various redox-active molecules from subcellular compartments to live organisms. In the first section of this review, we overview the background, focusing on the sensing mechanisms of various GERIs. Next, we review a list of selected GERIs according to their analytical targets and discuss their key biophysical and biochemical properties. In the third section, we provide several examples which applied GERIs to understanding redox signaling and oxidative toxicology in pathophysiological processes. Lastly, a summary and outlook section is included.
氧化还原活性分子在细胞内稳态、信号转导和其他生物过程中发挥着重要作用。氧化还原信号的失调会导致毒性作用,并随后导致疾病。因此,实时跟踪活细胞中特定的氧化还原信号分子对于破译它们在病理生理学中的功能作用至关重要。基于荧光蛋白(FP)的基因编码氧化还原指示剂(GERIs)已成为监测各种氧化还原活性分子从亚细胞区室到活体的氧化还原状态的有价值的工具。在本综述的第一部分中,我们概述了背景,重点介绍了各种 GERIs 的传感机制。接下来,我们根据分析目标综述了一系列选定的 GERIs,并讨论了它们的关键生物物理和生化特性。在第三部分中,我们提供了一些应用 GERIs 来理解病理生理过程中的氧化还原信号和氧化毒性的例子。最后,包括一个总结和展望部分。