Key Laboratory of Bioinorganicand Synthetic Chemistry of Ministry of Education, School of Chemistry, IGCME, GBRCE for Functional Molecular Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
Key Laboratory of Bioinorganicand Synthetic Chemistry of Ministry of Education, School of Chemistry, IGCME, GBRCE for Functional Molecular Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
Bioorg Med Chem. 2024 Sep 1;111:117856. doi: 10.1016/j.bmc.2024.117856. Epub 2024 Jul 23.
Mitochondrial G-quadruplexes are components that are potentially involved in regulating mitochondrial function and play crucial roles in the replication and transcription of mitochondrial genes. Consequently, it is imperative to develop probes that can detect mitochondrial G-quadruplexes to understand their functions and mechanisms. In this study, a triphenylamine fluorescent probe, TPPE, which has excellent cytocompatibility and does not affect the natural state of G-quadruplexes, was designed and demonstrated to localize primarily to the mitochondria. Owing to the unique binding mode between TPPE and G-quadruplexes, TPPE was able to distinguish G-quadruplexes from other substances due to the higher fluorescence lifetime and quantum yield. On the basis of the photon counts determined via fluorescence lifetime imaging microscopy, we analyzed the differences in the numbers of mitochondrial G-quadruplexes in various cell lines. We observed reductions in the number of mitochondrial G-quadruplexes during apoptosis, ferroptosis and glycolysis inhibition. This study shows the great potential of using TPPE to track and analyze mitochondrial G-quadruplexes and presents a novel perspective in the development of probes to detect mitochondrial G-quadruplexes in live cells.
线粒体 G-四链体是潜在参与调节线粒体功能的组成部分，在线粒体基因的复制和转录中发挥着关键作用。因此，开发能够检测线粒体 G-四链体的探针来了解其功能和机制是至关重要的。在这项研究中，设计并证明了一种具有优异细胞相容性且不影响 G-四链体天然状态的三苯胺荧光探针 TPPE，主要定位于线粒体。由于 TPPE 与 G-四链体之间的独特结合模式，TPPE 能够区分 G-四链体与其他物质，因为它具有更高的荧光寿命和量子产率。基于荧光寿命成像显微镜确定的光子计数，我们分析了各种细胞系中线粒体 G-四链体数量的差异。我们观察到在细胞凋亡、铁死亡和糖酵解抑制过程中，线粒体 G-四链体的数量减少。这项研究表明，使用 TPPE 来追踪和分析线粒体 G-四链体具有很大的潜力，并为在活细胞中检测线粒体 G-四链体的探针开发提供了新的视角。
