Subscribe to RSS
DOI: 10.1055/a-2522-0571
Phototriggered Migration of Indole-Based Cationic Fluorophore from Mitochondria to Nucleolus in Live Cells
This project was funded by Council of Scientific and Industrial Research (CSIR), New Delhi entitled ‘Targeting RNA Driven Processes: Novel Chemical Biology Approaches to Identify New Classes of RNA Modulators’ (MLP-139). Aakriti Garg thanks the National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata and the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers (MoCF), India for providing the institutional fellowship. Subhankar Singha acknowledges the research funding from the Science and Engineering Research Board (SERB), Govt. of India (Grant No: CRG/2022/008799).
Abstract
Small-molecule fluorescence probes capable of migrating between subcellular organelles under varying cellular conditions are essential tools for investigating live cell events. In this work, we present TNK-01, synthesized from pyridinium salt and indole derivatives known for their affinity to nucleic acids and ability to target mitochondria. TNK-01 exhibits migration from mitochondria to the nucleolus upon continuous light irradiation, driven by its differential binding affinities for the negatively charged mitochondrial membrane and RNA. The photo-triggered migration of TNK-01 is enhanced by its RNA binding affinity, resulting in an approximate 32-fold increase in fluorescent signal with selectivity for RNA over DNA. Furthermore, TNK-01 demonstrates stable emission across a pH range of 3 to 8, allowing for effective monitoring of translocation across various cell lines. Its large Stokes shift, high photostability, wash-free imaging, and low cytotoxicity make TNK-01 a promising tool for cellular imaging in live cells. This photo-triggered indole-based fluorescent probe enables new research in mitochondrial studies and organelle communication, which are increasingly important for understanding metabolism and disease progression.
Key words
indole - RNA binding - fluorescence probe migration - mitochondria - nucleolus - light irradiation - wash-freeSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2522-0571.
- Supporting Information
Publication History
Received: 21 November 2024
Accepted after revision: 21 January 2025
Accepted Manuscript online:
21 January 2025
Article published online:
07 March 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References and Notes
- 1 Li MY, Liu YH, Li K, Zhang H, Shi L, Liu XY, Yu KK, Yu XQ. Analytical Methods 2019; 11: 5750
- 2 Roy SS, Hajnóczky G. Methods 2008; 46: 213
- 3 Wang Y, Lin Q, Liu Y, Li C, Liu Z, Yu X, Wang K.-N. Anal. Chem. 2024; 96: 9808
- 4 Tian M, Ma Y, Lin W. Acc. Chem. Res. 2019; 52: 2147
- 5 Xiao A, Gibbons AE, Luker KE, Luker GD. Tomography 2015; 1: 115
- 6 Correll CC, Bartek J, Dundr M. Cells 2019; 8: 869
- 7 Dubois M.-L, Boisvert F.-M. The Nucleolus: Structure and Function . In The Functional Nucleus . Bazett-Jones DP, Dellaire G. Springer International; Switzerland: 2016: 29
- 8 Jiao L, Liu Y, Yu X.-Y, Pan X, Zhang Y, Tu J, Song Y.-H, Li Y. Signal Transduct. Target. Ther. 2023; 8: 15
- 9 Gutschner T, Diederichs S. RNA Biol. 2012; 9: 703
- 10 Modi S, López-Doménech G, Halff EF, Covill-Cooke C, Ivankovic D, Melandri D, Arancibia-Cárcamo IL, Burden JJ, Lowe AR, Kittler JT. Nat. Commun. 2019; 10: 4399
- 11 Lea PJ, Hollenberg MJ. Am. J. Anat. 1989; 184: 245
- 12 Somlyo AP, Somlyo AV, Devine CE, Peters PD, Hall TA. J. Cell Biol. 1974; 61: 723
- 13 Samanta S, He Y, Sharma A, Kim J, Pan W, Yang Z, Li J, Yan W, Liu L, Qu J, Kim JS. Chem 2019; 5: 1697
- 14 Xu J, Pan J, Jiang X, Qin C, Zeng L, Zhang H, Zhang JF. Biosens. Bioelectron. 2016; 77: 725
- 15 Neikirk K, Marshall AG, Kula B, Smith N, LeBlanc S, Hinton AJr. Eur. J. Cell Biol. 2023; 102: 151371
- 16 Chu Y, Park J, Kim E, Lee S. Materials 2021; 14: 4180
- 17 Binet M, Doyle C, Williamson J, Schlegel P. J. Exp. Mar. Biol Ecol. 2014; 452: 91
- 18 Karakaş D, Ari F, Ulukaya E. Turkish J. Biol. 2017; 41: 919
- 19 Wang KN, Liu LY, Qi G, Chao XJ, Ma W, Yu Z, Pan Q, Mao ZW, Liu B. Adv. Sci. 2021; 8: 2004379
- 20 Tian M, Sun J, Dong B, Lin W. Sens. Actuators, B 2019; 292: 16
- 21 Ge E, Tian M, Lin W. Sens. Actuators, B 2021; 347: 130656
- 22 Li X, Tian M, Zhang G, Zhang R, Feng R, Guo L, Yu X, Zhao N, He X. Anal. Chem. 2017; 89: 3335
- 23 Niu J, Meng F, Hao Q, Zong C, Fu J, Xue H, Tian M, Yu X. Anal. Chem. 2022; 94: 17885
- 24 Zhu X, Liu G, Bu Y, Zhang J, Wang L, Tian Y, Yu J, Wu Z, Zhou H. Anal. Chem. 2020; 92: 10815
- 25 Roehlecke C, Schaller A, Knels L, Funk RH. Mol. Vision 2009; 15: 1929
- 26 Zhuang J, Liu Y, Yuan Q, Liu J, Liu Y, Li H, Wang D. Oncol. Lett. 2018; 15: 6291
- 27 Gottlieb E, Armour S, Harris M, Thompson C. Cell Death Differ. 2003; 10: 709
- 28 Guo L, Chan MS, Xu D, Tam DY, Bolze F, Lo PK, Wong MS. ACS Chem. Biol. 2015; 10: 1171
- 29 Antoni PW, Bruckhoff T, Hansmann MM. J. Am. Chem. Soc. 2019; 141: 9701
- 30 Chen H, Wang J, Feng X, Zhu M, Hoffmann S, Hsu A, Qian K, Huang D, Zhao F, Liu W. Chem. Sci. 2019; 10: 7946
- 31 Brouwer AM. Pure Appl. Chem. 2011; 83: 2213
- 32 Yao Q, Li H, Xian L, Xu F, Xia J, Fan J, Du J, Wang J, Peng X. Biomaterials 2018; 177: 78
- 33 Wang L, Xia Q, Liu R, Qu J. Sens. Actuators, B 2018; 273: 935
- 34 Xue Z, Zhu R, Wang S, Li J, Han J, Liu J, Han S. Anal. Chem. 2018; 90: 2954
- 35 Garg A, Goel N, Abhinav N, Varma T, Achari A, Bhattacharjee P, Kamal IM, Chakrabarti S, Ravichandiran V, Reddy AM. J. Biomol. Struct. Dyn. 2023; 41: 2033
- 36 Prashanth T, Ranganatha VL, Ramu R, Mandal SP, Mallikarjunaswamy C, Khanum SA. J. Iran. Chem. Soc. 2021; 18: 2741
- 37 Kumar S, Singh J, Narasimhan B, Shah SA. A, Lim SM, Ramasamy K, Mani V. Chem. Cent. J. 2018; 12: 1
- 38 Gabdulkhakov A, Tishchenko S, Mikhaylina A, Garber M, Nevskaya N, Nikonov S. Crystals 2017; 7: 37
- 39 Delgado JL, Vance NR, Kerns RJ. Crystal Structure of DNA Dodecamer D(CGCGAATTCGCG). National Institutes of Health/National Institute of Allergy and Infectious Diseases. 2018, DOI: https://doi.org/10.2210/pdb6CQ3/pdb.
- 40 Li Q, Chang Y.-T. Nat. Protoc. 2006; 1: 2922
- 41 Fillingame RH, Angevine CM, Dmitriev OY. FEBS Lett. 2003; 555: 29
- 42 Wäldchen S, Lehmann J, Klein T, van de Linde S, Sauer M. Sci. Rep. 2015; 5: 15348
- 43 Douthwright S, Sluder G. J. Cell. Physiol. 2017; 232: 2461
- 44 Plumb JA. Cancer Cell Culture: Methods and Protocols . Langdon SP. Humana Press; Totowa, NJ: 2004: 165-169
- 45 Lindhagen E, Nygren P, Larsson R. Nat. Protoc. 2008; 3: 1364
- 46 Aslantürk ÖS. In Genotoxicity – A Predictable Risk to Our Actual World [Online]. Larramedy ML, Soloneski S. IntechOpen; London: 2018.