Institut Curie, Université PSL, CNRS UMR9187, Inserm U1196, Chemistry and Modelling for the Biology of Cancer, 91400, Orsay, France.
Université Paris-Saclay, CNRS UMR9187, Inserm U1196, Chemistry and Modelling for the Biology of Cancer, 91400, Orsay, France.
Chembiochem. 2021 Jul 15;22(14):2457-2467. doi: 10.1002/cbic.202100168. Epub 2021 Jun 2.
Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood. In this context, we synthesized analogues of the TP-2Bzim probe belonging to the vinyltriphenylamine (TPA) class and already described for its capacity to bind nuclear DNA in fixed cells and mitochondria in live cells. These analogues (TP-1Bzim, TP -2Bzim, TP -2Bzim, TN-2Bzim) differ in the cationic charge, the number of vinylbenzimidazolium branches and the nature of the triaryl core. Using microscopy, we demonstrated that the cationic derivatives accumulate in mitochondria but do not reach mtDNA. Under depolarisation of the mitochondrial membrane, TP-2Bzim and TP -2Bzim translocate to the nucleus in direct correlation with their strong DNA affinity. This reversible phenomenon emphasizes that these probes can be used to monitor ΔΨ variations.
线粒体参与许多细胞途径，功能失调的线粒体与各种疾病有关。因此，人们努力设计靶向线粒体的荧光染料来监测线粒体状态。然而，目前尚不清楚影响染料靶向线粒体能力的因素。在这方面，我们合成了属于乙烯基三苯胺（TPA）类的 TP-2Bzim 探针类似物，该探针已被描述为能够在固定细胞中结合核 DNA 和活细胞中的线粒体。这些类似物（TP-1Bzim、TP-2Bzim、TP-2Bzim、TN-2Bzim）在阳离子电荷、乙烯基苯并咪唑支链的数量和三芳基核心的性质上有所不同。通过显微镜观察，我们证明阳离子衍生物在线粒体中积累，但无法到达 mtDNA。在线粒体膜去极化时，TP-2Bzim 和 TP-2Bzim 与它们与 DNA 的强亲和力一起转位到细胞核。这种可逆现象强调了这些探针可用于监测 ΔΨ 变化。
